1.
BRENDA
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BRENDA is an information system representing one of the most comprehensive enzyme repositories. It is a resource that comprises molecular and biochemical information on enzymes that have been classified by the IUBMB. Every classified enzyme is characterized with respect to its catalyzed biochemical reaction, kinetic properties of the corresponding reactants are described in detail. BRENDA contains enzyme-specific data manually extracted from scientific literature and additional data derived from automatic information retrieval methods such as text mining. It provides a user interface that allows a convenient and sophisticated access to the data. BRENDA was founded in 1987 at the former German National Research Centre for Biotechnology in Braunschweig and was published as a series of books. Its name was originally an acronym for the Braunschweig Enzyme Database, from 1996 to 2007, BRENDA was located at the University of Cologne. There, BRENDA developed into a publicly accessible enzyme information system, in 2007, BRENDA returned to Braunschweig. Currently, BRENDA is maintained and further developed at the Department of Bioinformatics, a major update of the data in BRENDA is performed twice a year. Besides the upgrade of its content, improvements of the interface are also incorporated into the BRENDA database. The latest update was performed in January 2015, Database, The database contains more than 40 data fields with enzyme-specific information on more than 7000 EC numbers that are classified according to the IUBMB. Currently, BRENDA contains manually annotated data from over 140,000 different scientific articles, each enzyme entry is clearly linked to at least one literature reference, to its source organism, and, where available, to the protein sequence of the enzyme. An important part of BRENDA represent the more than 110,000 enzyme ligands, the term ligand is used in this context to all low molecular weight compounds which interact with enzymes. These include not only metabolites of primary metabolism, co-substrates or cofactors, the origin of these molecules ranges from naturally occurring antibiotics to synthetic compounds that have been synthesized for the development of drugs or pesticides. Furthermore, cross-references to external resources such as sequence and 3D-structure databases. Extensions, Since 2006, the data in BRENDA is supplemented with information extracted from the literature by a co-occurrence based text mining approach. For this purpose, four text-mining repositories FRENDA, AMENDA, DRENDA and KENDA were introduced and these text-mining results were derived from the titles and abstracts of all articles in the literature database PubMed. Data access, There are several tools to access to the data in BRENDA
2.
MetaCyc
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The MetaCyc database contains extensive information on metabolic pathways and enzymes from many organisms. MetaCyc is also used in engineering and metabolomics research. MetaCyc contains extensive data on individual enzymes, describing their subunit structure, cofactors, activators and inhibitors, substrate specificity, MetaCyc data on reactions includes predicted atom mappings that describe the correspondence between atoms in the reactant compounds and the product compounds. It also provides enzyme mini-reviews and literature references, MetaCyc data on metabolites includes chemical structures, predicted Gibbs free energies of formation, and links to external databases
3.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
4.
PubMed
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
5.
National Center for Biotechnology Information
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The National Center for Biotechnology Information is part of the United States National Library of Medicine, a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper, the NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. Major databases include GenBank for DNA sequences and PubMed, a database for the biomedical literature. Other databases include the NCBI Epigenomics database, all these databases are available online through the Entrez search engine. NCBI is directed by David Lipman, one of the authors of the BLAST sequence alignment program. He also leads a research program, including groups led by Stephen Altschul, David Landsman, Eugene Koonin, John Wilbur, Teresa Przytycka. NCBI is listed in the Registry of Research Data Repositories re3data. org, NCBI has had responsibility for making available the GenBank DNA sequence database since 1992. GenBank coordinates with individual laboratories and other databases such as those of the European Molecular Biology Laboratory. Since 1992, NCBI has grown to other databases in addition to GenBank. The NCBI assigns a unique identifier to each species of organism, the NCBI has software tools that are available by WWW browsing or by FTP. For example, BLAST is a sequence similarity searching program, BLAST can do sequence comparisons against the GenBank DNA database in less than 15 seconds. RAG2/IL2RG The NCBI Bookshelf is a collection of freely accessible, downloadable, some of the books are online versions of previously published books, while others, such as Coffee Break, are written and edited by NCBI staff. BLAST is a used for calculating sequence similarity between biological sequences such as nucleotide sequences of DNA and amino acid sequences of proteins. BLAST is a tool for finding sequences similar to the query sequence within the same organism or in different organisms. It searches the query sequence on NCBI databases and servers and post the results back to the browser in chosen format. Input sequences to the BLAST are mostly in FASTA or Genbank format while output could be delivered in variety of such as HTML, XML formatting. HTML is the output format for NCBIs web-page. Entrez is both indexing and retrieval system having data from sources for biomedical research
6.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
7.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
8.
Chemical reaction
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A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Nuclear chemistry is a sub-discipline of chemistry that involves the reactions of unstable. The substance initially involved in a reaction are called reactants or reagents. Chemical reactions are characterized by a chemical change, and they yield one or more products. Reactions often consist of a sequence of individual sub-steps, the elementary reactions. Chemical reactions are described with chemical equations, which present the starting materials, end products. Chemical reactions happen at a characteristic reaction rate at a given temperature, typically, reaction rates increase with increasing temperature because there is more thermal energy available to reach the activation energy necessary for breaking bonds between atoms. Reactions may proceed in the forward or reverse direction until they go to completion or reach equilibrium, Reactions that proceed in the forward direction to approach equilibrium are often described as spontaneous, requiring no input of free energy to go forward. Non-spontaneous reactions require input of energy to go forward. Different chemical reactions are used in combinations during chemical synthesis in order to obtain a desired product, in biochemistry, a consecutive series of chemical reactions form metabolic pathways. These reactions are catalyzed by protein enzymes. Chemical reactions such as combustion in fire, fermentation and the reduction of ores to metals were known since antiquity, in the Middle Ages, chemical transformations were studied by Alchemists. They attempted, in particular, to lead into gold, for which purpose they used reactions of lead. The process involved heating of sulfate and nitrate minerals such as sulfate, alum. In the 17th century, Johann Rudolph Glauber produced hydrochloric acid and sodium sulfate by reacting sulfuric acid, further optimization of sulfuric acid technology resulted in the contact process in the 1880s, and the Haber process was developed in 1909–1910 for ammonia synthesis. From the 16th century, researchers including Jan Baptist van Helmont, Robert Boyle, the phlogiston theory was proposed in 1667 by Johann Joachim Becher. It postulated the existence of an element called phlogiston, which was contained within combustible bodies. This proved to be false in 1785 by Antoine Lavoisier who found the explanation of the combustion as reaction with oxygen from the air
9.
Product (chemistry)
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Products are the species formed from chemical reactions. During a chemical reaction reactants are transformed into products after passing through an energy transition state. This process results in the consumption of the reactants, when represented in chemical equations products are by convention drawn on the right-hand side, even in the case of reversible reactions. The properties of such as their energies help determine several characteristics of a chemical reaction such as whether the reaction is exergonic or endergonic. Additionally the properties of a product can make it easier to extract and purify following a chemical reaction, reactants are molecular materials used to create chemical reactions. The atoms arent created or destroyed, the materials are reactive and reactants are rearranging during a chemical reaction. Here is an example of reactants, CH4 + O2, a non-example is CO2 + H2O or energy. Much of chemistry research is focused on the synthesis and characterization of beneficial products, as well as the detection, other fields include natural product chemists who isolate products created by living organisms and then characterize and study these products. The products of a chemical reaction influence several aspects of the reaction, if the products are lower in energy than the reactants, then the reaction will give off excess energy making it an exergonic reaction. Such reactions are thermodynamically favorable and tend to happen on their own, if the kinetics of the reaction are high enough, however, then the reaction may occur too slowly to be observed, or not even occur at all. If the products are higher in energy than the reactants then the reaction will require energy to be performed and is therefore an endergonic reaction. Additionally if the product is less stable than a reactant, then Lefflers assumption holds that the state will more closely resemble the product than the reactant. Ever since the mid nineteenth century chemists have been preoccupied with synthesizing chemical products. Much of synthetic chemistry is concerned with the synthesis of new chemicals as occurs in the design and creation of new drugs, in biochemistry, enzymes act as biological catalysts to convert substrate to product. For example, the products of the enzyme lactase are galactose and glucose, S + E → P + E Where S is substrate, P is product and E is enzyme. Some enzymes display a form of promiscuity where they convert a single substrate into multiple different products and it occurs when the reaction occurs via a high energy transition state that can be resolved into a variety of different chemical products. Some enzymes are inhibited by the product of their reaction binds to the enzyme and this can be important in the regulation of metabolism as a form of negative feedback controlling metabolic pathways. Product inhibition is also an important topic in biotechnology, as overcoming this effect can increase the yield of a product, Chemical reaction Substrate Reagent Precursor Catalyst Enzyme Product Derivative Chemical equilibrium Second law of thermodynamics
10.
Glycosyltransferase
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Glycosyltransferases are enzymes that establish natural glycosidic linkages. The result of transfer can be a carbohydrate, glycoside, oligosaccharide. Some glycosyltransferases catalyse transfer to inorganic phosphate or water, glycosyl transfer can also occur to protein residues, usually to tyrosine, serine, or threonine to give O-linked glycoproteins, or to asparagine to give N-linked glycoproteins. Mannosyl groups may be transferred to tryptophan to generate C-mannosyl tryptophan, transferases may also use lipids as an acceptor, forming glycolipids, and even use lipid-linked sugar phosphate donors, such as dolichol phosphates. Glycosyltransferases that utilize non-nucleotide donors such as dolichol or polyprenol pyrophosphate are non-Leloir glycosyltransferases, the phosphate of these donor molecules are usually coordinated by divalent cations such as manganese, however metal independent enzymes exist. Glycosyltransferases can be segregated into “retaining” or“ inverting” enzymes according to whether the stereochemistry of the donor’s anomeric bond is retained or inverted during the transfer, the inverting mechanism is straightforward, requiring a single nucleophilic attack from the accepting atom to invert stereochemistry. The retaining mechanism has been a matter of debate, but there exists strong evidence against a double displacement mechanism or a dissociative mechanism, sequence-based classification methods have proven to be a powerful way of generating hypotheses for protein function based on sequence alignment to related proteins. The carbohydrate-active enzyme database presents a classification of glycosyltransferases into over 90 families. The same three-dimensional fold is expected to occur within each of the families, in contrast to the diversity of 3D structures observed for glycoside hydrolases, glycosyltransferase have a much smaller range of structures. Many inhibitors of glycosyltransferases are known, some glycosyltransferase inhibitors are of use as drugs or antibiotics. Moenimycin is used in animal feed as a growth promoter, caspofungin has been developed from the echinocandins and is in use as an antifungal agent. Ethambutol is an inhibitor of mycobacterial arabinotransferases and is used for the treatment of tuberculosis, lufenuron is an inhibitor of insect chitin synthases and is used to control fleas in animals. The ABO blood group system is determined by type of glucosyltransferases are expressed in the body. The ABO gene locus expressing the glucosyltransferases has three main forms, A, B, and O. The A allele encodes 1-3-N-acetylgalactosaminyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, the B allele encodes 1-3-galactosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen. In case of O allele the exon 6 contains a deletion that results in a loss of enzymatic activity, the O allele differs slightly from the A allele by deletion of a single nucleotide - Guanine at position 261. The deletion causes a frameshift and results in translation of an almost entirely different protein that lacks enzymatic activity and this results in H antigen remaining unchanged in case of O groups. The combination of glucosyltransferases by both present in each person determines whether there is an AB, A, B or O blood type
11.
International Standard Book Number
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The International Standard Book Number is a unique numeric commercial book identifier. An ISBN is assigned to each edition and variation of a book, for example, an e-book, a paperback and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, the method of assigning an ISBN is nation-based and varies from country to country, often depending on how large the publishing industry is within a country. The initial ISBN configuration of recognition was generated in 1967 based upon the 9-digit Standard Book Numbering created in 1966, the 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108. Occasionally, a book may appear without a printed ISBN if it is printed privately or the author does not follow the usual ISBN procedure, however, this can be rectified later. Another identifier, the International Standard Serial Number, identifies periodical publications such as magazines, the ISBN configuration of recognition was generated in 1967 in the United Kingdom by David Whitaker and in 1968 in the US by Emery Koltay. The 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108, the United Kingdom continued to use the 9-digit SBN code until 1974. The ISO on-line facility only refers back to 1978, an SBN may be converted to an ISBN by prefixing the digit 0. For example, the edition of Mr. J. G. Reeder Returns, published by Hodder in 1965, has SBN340013818 -340 indicating the publisher,01381 their serial number. This can be converted to ISBN 0-340-01381-8, the check digit does not need to be re-calculated, since 1 January 2007, ISBNs have contained 13 digits, a format that is compatible with Bookland European Article Number EAN-13s. An ISBN is assigned to each edition and variation of a book, for example, an ebook, a paperback, and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, a 13-digit ISBN can be separated into its parts, and when this is done it is customary to separate the parts with hyphens or spaces. Separating the parts of a 10-digit ISBN is also done with either hyphens or spaces, figuring out how to correctly separate a given ISBN number is complicated, because most of the parts do not use a fixed number of digits. ISBN issuance is country-specific, in that ISBNs are issued by the ISBN registration agency that is responsible for country or territory regardless of the publication language. Some ISBN registration agencies are based in national libraries or within ministries of culture, in other cases, the ISBN registration service is provided by organisations such as bibliographic data providers that are not government funded. In Canada, ISBNs are issued at no cost with the purpose of encouraging Canadian culture. In the United Kingdom, United States, and some countries, where the service is provided by non-government-funded organisations. Australia, ISBNs are issued by the library services agency Thorpe-Bowker
12.
Transferase
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A transferase is any one of a class of enzymes that enact the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, transferases are involved in myriad reactions in the cell. Transferases are also utilized during translation, in this case, an amino acid chain is the functional group transferred by a peptidyl transferase. Group would be the group transferred as a result of transferase activity. The donor is often a coenzyme, some of the most important discoveries relating to transferases occurred as early as the 1930s. Earliest discoveries of transferase activity occurred in other classifications of enzymes, including Beta-galactosidase, protease, prior to the realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers. This observance was later verified by the discovery of its reaction mechanism by Braunstein and their analysis showed that this reversible reaction could be applied to other tissues. This assertion was validated by Rudolf Schoenheimers work with radioisotopes as tracers in 1937 and this in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer. Another such example of early research and later reclassification involved the discovery of uridyl transferase. In 1953, the enzyme UDP-glucose pyrophosphorylase was shown to be a transferase, when it was found that it could reversibly produce UTP and G1P from UDP-glucose, another example of historical significance relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This discovery was a part of the reason for Julius Axelrod’s 1970 Nobel Prize in Physiology or Medicine. Classification of transferases continues to this day, with new ones being discovered frequently, an example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of Drosophilia. Initially, the mechanism of Pipe was unknown, due to a lack of information on its substrate. Research into Pipes catalytic activity eliminated the likelihood of it being a heparan sulfate glycosaminoglycan, further research has shown that Pipe targets the ovarian structures for sulfation. Pipe is currently classified as a Drosophilia heparan sulfate 2-O-sulfotransferase, systematic names of transferases are constructed in the form of donor, acceptor grouptransferase. For example, a DNA methyltransferase is a transferase that catalyzes the transfer of a group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names, in the EC system of classification, the accepted name for RNA Polymerase is DNA-directed RNA polymerase. Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories and these categories comprise over 450 different unique enzymes
13.
Glycogen phosphorylase
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Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1, Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects. Glycogen phosphorylase breaks up glycogen into glucose subunits, n + Pi ⇌ n-1 + α-D-glucose-1-phosphate, Glycogen is left with one fewer glucose molecule, and the free glucose molecule is in the form of glucose-1-phosphate. In order to be used for metabolism, it must be converted to glucose-6-phosphate by the enzyme phosphoglucomutase, Glycogen phosphorylase can act only on linear chains of glycogen. Its work will come to a halt four residues away from α1-6 branch. In these situations, an enzyme is necessary, which will straighten out the chain in that area. After all this is done, glycogen phosphorylase can continue and this crevice connects the glycogen storage site to the active, catalytic site. Glycogen phosphorylase has a pyridoxal phosphate at each catalytic site, pyridoxal phosphate links with basic residues and covalently forms a Schiff base. There is also a proposed mechanism involving a positively charged oxygen in a half-chair conformation. The glycogen phosphorylase monomer is a protein, composed of 842 amino acids with a mass of 97.434 kDa in muscle cells. While the enzyme can exist as a monomer or tetramer. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver, the brain type is predominant in adult brain and embryonic tissues, whereas the liver and muscle types are predominant in adult liver and skeletal muscle, respectively. The glycogen phosphorylase dimer has many regions of biological significance, including sites, glycogen binding sites, allosteric sites. First, the sites are relatively buried, 15Å from the surface of the protein. Perhaps the most important regulatory site is Ser14, the site of reversible phosphorylation very close to the subunit interface. The structural change associated with phosphorylation, and with the conversion of phosphorylase b to phosphorylase a, is the arrangement of the originally disordered residues 10 to 22 into α helices. This change increases phosphorylase activity up to 25% even in the absence of AMP, the allosteric site of AMP binding on muscle isoforms of glycogen phosphorylase are close to the subunit interface just like Ser14. AMP binding rotates the tower helices of the two subunits 50˚ relative to one another through greater organization and intersubunit interactions, the final, perhaps most curious site on the glycogen phosphorylase protein is the so-called glycogen storage site
14.
Myophosphorylase
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Myophosphorylase is the muscle isoform of the enzyme glycogen phosphorylase. This enzyme helps break down glycogen into glucose-1-phosphate, so that it can be utilized within the muscle cell, a deficiency is associated with Glycogen storage disease type V, also known as McArdles Syndrome. A case study suggested that a deficiency in myophosphorylase may be linked with cognitive impairment, besides muscle, this isoform is present in astrocytes, where it plays a key role in neural energy metabolism. A 55-year-old woman with McArdle disease has expressed cognitive impairment with bilateral dysfunction of prefrontal and frontal cortex, further studies are needed to assess the validity of this claim. Myophosphorylase at the US National Library of Medicine Medical Subject Headings
15.
Glycogen synthase
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Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP, in other words, this enzyme combines excess glucose residues one by one into a polymeric chain for storage as glycogen. Glycogen synthase concentration is highest in the bloodstream 30 to 60 minutes following intense exercise, much research has been done on glycogen degradation through studying the structure and function of glycogen phosphorylase, the key regulatory enzyme of glycogen degradation. On the other hand, much less is known about the structure of glycogen synthase, the crystal structure of glycogen synthase from Agrobacterium tumefaciens, however, has been determined at 2.3 A resolution. In its asymmetric form, glycogen synthase is found as a dimer and this structural property, among others, is shared with related enzymes, such as glycogen phosphorylase and other glycosyltransferases of the GT-B superfamily. Nonetheless, a more recent characterization of the Saccharomyces cerevisiae glycogen synthase crystal structure reveals that the dimers may actually interact to form a tetramer, since the structure of eukaryotic glycogen synthase is highly conserved among species, glycogen synthase likely forms a tetramer in humans as well. Glycogen synthase can be classified in two protein families. The first family, which is from mammals and yeast, is approximately 80 kDa, uses UDP-glucose as a sugar donor, the second family, which is from bacteria and plants, is approximately 50 kDA, uses ADP-glucose as a sugar donor, and is unregulated. Glycogen synthase catalyzes the conversion of the moiety of uridine diphosphate glucose into glucose to be incorporated into glycogen via an α glycosidic bond. However, since glycogen synthase requires an oligosaccharide primer as a glucose acceptor, in a recent study of transgenic mice, an overexpression of glycogen synthase and an overexpression of phosphatase both resulted in excess glycogen storage levels. This suggests that glycogen synthase plays an important biological role in regulating glycogen/glucose levels and is activated by dephosphorylation, in humans, there are two paralogous isozymes of glycogen synthase, The liver enzyme expression is restricted to the liver, whereas the muscle enzyme is widely expressed. Liver glycogen serves as a pool to maintain the blood glucose level during fasting. The role of muscle glycogen is as a reserve to provide energy during bursts of activity, meanwhile, the muscle isozyme plays a major role in the cellular response to long-term adaptation to hypoxia. Notably, hypoxia only induces expression of the muscle isozyme and not the liver isozyme, however, muscle-specific glycogen synthase activation may lead to excessive accumulation of glycogen, leading to damage in the heart and central nervous system following ischemic insults. Phosphorylation of glycogen synthase decreases its activity, the enzyme also cleaves the ester bond between the C1 position of glucose and the pyrophosphate of UDP itself. The control of glycogen synthase is a key step in regulating glycogen metabolism, glycogen synthase is directly regulated by glycogen synthase kinase 3, AMPK, protein kinase A, and casein kinase 2. Each of these protein kinases lead to phosphorylated and catalytically inactive glycogen synthase, the phosphorylation sites of glycogen synthase are summarized below. For enzymes in the GT3 family, these regulatory kinases inactivate glycogen synthase by phosphorylating it at the N-terminal of the 25th residue, glycogen synthase is also regulated by protein phosphatase 1, which activates glycogen synthase via dephosphorylation
16.
Glycogen debranching enzyme
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A debranching enzyme is a molecule that helps facilitate the breakdown of glycogen, which serves as a store of glucose in the body, through glucosyltransferase and glucosidase activity. Together with phosphorylases, debranching enzymes mobilize glucose reserves from glycogen deposits in the muscles and this constitutes a major source of energy reserves in most organisms. Glycogen breakdown is highly regulated in the body, especially in the liver, by various hormones including insulin and glucagon, when glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as Glycogen storage disease type III can result. Glucosyltransferase and glucosidase are performed by an enzyme in mammals, yeast, and some bacteria. Proteins that catalyze both functions are referred to as glycogen debranching enzymes, when glucosyltransferase and glucosidase are catalyzed by distinct enzymes, glycogen debranching enzyme usually refers to the glucosidase enzyme. In some literature, an enzyme capable only of glucosidase is referred to as a debranching enzyme, together with phosphorylase, glycogen debranching enzymes function in glycogen breakdown and glucose mobilization. When phosphorylase has digested a glycogen branch down to four glucose residues, Glycogen debranching enzymes assist phosphorylase, the primary enzyme involved in glycogen breakdown, mobilize glycogen stores. Phosphorylase can only cleave α-1, 4- glycosidic bond between adjacent glucose molecules in glycogen but branches exist as α-1,6 linkages. The mechanism by which the glucosidase cleaves the α -1, 6-linkage is not fully known because the amino acids in the site have not yet been identified. It is thought to proceed through a two step acid base assistance type mechanism, with an oxocarbenium ion intermediate, and retention of configuration in glucose. This is a method through which to cleave bonds, with an acid below the site of hydrolysis to lend a proton. These acids and bases are amino acid chains in the active site of the enzyme. A scheme for the mechanism is shown in the figure below, thus the debranching enzymes, transferase and α-1, 6- glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase. In E. coli and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct enzymes, in E. coli, Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ. A second protein, referred to as debranching enzyme, performs α-1 and this enzyme has a molecular mass of 73.6 kDa, and is coded for by the gene glgX. Activity of the two enzymes is not always necessarily coupled, in E. coli glgX selectively catalyzes the cleavage of 4-subunit branches, without the action of glucanotransferase. The product of cleavage, maltotetraose, is further degraded by maltodextrin phosphorylase. E. coli GlgX is structurally similar to the protein isoamylase, the monomeric protein contains a central domain in which eight parallel beta-strands are surrounded by eight parallel alpha strands
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Glycogen branching enzyme
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Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecule during the synthesis of glycogen, a storage form of glucose. More specifically, during synthesis, a glucose 1-phosphate molecule reacts with uridine triphosphate to become UDP-glucose. Importantly, glycogen synthase can only catalyze the synthesis of α-1, branching also importantly increases the solubility and decreases the osmotic strength of glycogen. This enzyme belongs to the family of transferases, to be specific, the systematic name of this enzyme class is 1, 4-alpha-D-glucan,1, 4-alpha-D-glucan 6-alpha-D--transferase. This enzyme participates in starch and sucrose metabolism, GBE is encoded by the GBE1 gene. Through southern blot analysis of DNA derived from human/rodent somatic cell hybrids, the human GBE gene was also isolated by a function complementation of the Saccharomyces cerevisiae GBE deficiency. From the isolated cDNA, the length of the gene was found to be approximately 3 kb, additionally, the coding sequence was found to comprise 2,106 base pairs and encode a 702-amino acid long GBE. The molecular mass of human GBE was calculated to be 80,438 Da, glycogen branching enzyme belongs to the α-amylase family of enzymes, which include α-amylases, pullulanas/isoamylase, cyclodextrin glucanotransferase, and branching enzyme. While the central domain is common in members of the α-amylase family. Additionally, there are striking differences between the loops connecting elements of the secondary structure among these various α-amylase members, especially around the active site. In comparison to the family members, glycogen binding enzyme has shorter loops. These residues are implicated in catalysis and substrate binding, glycogen binding enzymes in other organisms have also been crystallized and structurally determined, demonstrating both similarity and variation to GBE found in Escherichia coli. In glycogen, every 10 to 14 glucose units, a branch with an additional chain of glucose units occurs. The side chain attaches at carbon atom 6 of a glucose unit and this connection is catalyzed by a branching enzyme, generally given the name α-glucan branching enzyme. A branching enzyme attaches a string of seven glucose units to the carbon at the C-6 position on the unit, forming the α-1. The specific nature of this means that this chain of 7 carbons is usually attached to a glucose molecule that is in position three from the non-reducing end of another chain. Mutations in this gene are associated with glycogen storage disease type IV in newborns, approximately 40 mutations in the GBE1 gene, most resulting in a point mutation in the glycogen branching enzyme, have led to the early childhood disorder, glycogen storage disease type IV. This disease is characterized by a severe depletion or complete absence of GBE, resulting in the accumulation of abnormally structured glycogen, glycogen buildup leads to increased osmotic pressure resulting in cellular swelling and death
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Galactosyltransferase
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Galactosyltransferase is a type of glycosyltransferase which catalyzes the transfer of galactose. The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases and these enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. This classification is available on the CAZy web site, the same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form clans
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Glucuronosyltransferase
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Uridine 5-diphospho-glucuronosyltransferase is a cytosolic glycosyltransferase that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. Alternative names, glucuronyltransferase UDP-glucuronyl transferase UDP-GT Glucuronosyltransferases are responsible for the process of glucuronidation, arguably the most important of the Phase II enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. It is also the pathway for foreign chemical removal for most drugs, dietary substances, toxins. UGT is present in humans, other animals, plants, famously, UGT enzymes are not present in the genus Felis, and this accounts for a number of unusual toxicities in the cat family. The resulting glucuronide is more polar and more easily excreted than the substrate molecule, the product solubility in blood is increased allowing it to be eliminated from the body by the kidneys. A deficiency in the specific form of glucuronosyltransferase is thought to be the cause of Gilberts syndrome. It is also associated with Crigler-Najjar syndrome, a serious disorder where the enzymes activity is either completely absent or less than 10% of normal. Infants may have a deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol which requires glucuronidation. This leads to a known as gray baby syndrome
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B3GAT1
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Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1, or CD57, is an enzyme that in humans is encoded by the B3GAT1 gene. In immunology, the CD57 antigen is known as HNK1 or LEU7. It is expressed as an epitope that contains a sulfoglucuronyl residue in several adhesion molecules of the nervous system. The protein encoded by this gene is a member of the gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and this gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1. Alternate transcriptional splice variants have been characterized, in anatomical pathology, CD57 is similar to CD56 for use in differentiating neuroendocrine tumors from others. Using immunohistochemistry, CD57 molecule can be demonstrated in around 10 to 20% of lymphocytes, as well as in some epithelial, neural, and chromaffin cells. Among lymphocytes, CD57 positive cells are typically either T cells or NK cells, and are most commonly found within the germinal centres of lymph nodes, tonsils, increased CD57+ counts have also been reported in rheumatoid arthritis and Feltys syndrome, among other conditions. Neoplastic CD57 positive cells are seen in conditions as varied as large granular lymphocytic leukaemia, small-cell carcinoma, thyroid carcinoma, CD57 Antigen at the US National Library of Medicine Medical Subject Headings Human B3GAT1 genome location and B3GAT1 gene details page in the UCSC Genome Browser
