The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. SH3 was described as a conserved sequence in the viral adaptor protein v-Crk; this domain is present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, the Src kinase and many others; the SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases SH3 proteins bind far away from the active site. 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling; the SH3 domain has a characteristic beta-barrel fold that consists of five or six β-strands arranged as two packed anti-parallel β sheets.
The linker regions may contain short helices. The SH3-type fold; the classical SH3 domain is found in proteins that interact with other proteins and mediate assembly of specific protein complexes via binding to proline-rich peptides in their respective binding partner. Classical SH3 domains are restricted in humans to intracellular proteins, although the small human MIA family of extracellular proteins contain a domain with an SH3-like fold. Many SH3-binding epitopes of proteins have a consensus sequence that can be represented as a regular expression or Short linear motif: -X-P-p-X-P- 1 2 3 4 5 with 1 and 4 being aliphatic amino acids, 2 and 5 always and 3 sometimes being proline; the sequence binds to the hydrophobic pocket of the SH3 domain. More SH3 domains that bind to a core consensus motif R-x-x-K have been described. Examples are the C-terminal SH3 domains of adaptor proteins like Mona. Other SH3 binding motifs have emerged and are still emerging in the course of various molecular studies, highlighting the versatility of this domain.
SH3 domain mediated protein-protein interaction networks, i.e. SH3 interactomes, revealed that worm SH3 interactome resembles the analogous yeast network because it is enriched for proteins with roles in endocytosis. Orthologous SH3 domain-mediated interactions are rewired between worm and yeast. Signal transducing adaptor proteins CDC24 Cdc25 PI3 kinase Phospholipase Ras GTPase-activating protein Vav proto-oncogene GRB2 p54 S6 kinase 2 SH3D21 C10orf76 STAC3 Some myosins SHANK1,2,3 ARHGAP12 C8orf46 TANGO1 Integrase Focal Adhesion Kinase Proline-rich tyrosine kinase TRIP10 Src homology 2 domain-containing Structural domain Eukaryotic Linear Motif resource motif class LIG_SH3_1 Eukaryotic Linear Motif resource motif class LIG_SH3_2 Eukaryotic Linear Motif resource motif class LIG_SH3_3 Eukaryotic Linear Motif resource motif class LIG_SH3_4 Eukaryotic Linear Motif resource motif class LIG_SH3_5 Eukaryotic Linear Motif resource motif class TRG_PEX_1 Nash Lab Protein Interaction Domains in Signal Transduction - The SH3 domain GENEART - Screen your protein against all human SH3 domains in a single phage display cycle
Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on efficacy, they are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators enroll volunteers or patients into small pilot studies, subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, they can involve a single research center or multiple centers, in one country or in multiple countries.
Clinical study design aims to ensure the scientific reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug; the sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become an approved drug; some clinical trials involve healthy subjects with no pre-existing medical conditions. Other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment; when participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick. During dosing periods, study subjects remain under supervision for one to 40 nights. Pilot experiments are conducted to gain insights for design of the clinical trial to follow.
There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy" or "effectiveness". Neither is an absolute criterion; the benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care, are used for a life-threatening condition. In the US, the elderly constitute 14 % of the population. People over 55 are excluded from trials because their greater health issues and drug use complicate data interpretation, because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are frequently excluded. Pregnant women are excluded due to potential risks to the fetus; the sponsor designs the trial in coordination with a panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type of patients might benefit.
If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment and collect data on the subjects' health for a defined time period. Data include measurements such as vital signs, concentration of the study drug in the blood or tissues, changes to symptoms, whether improvement or worsening of the condition targeted by the study drug occurs; the researchers send the data to the trial sponsor, who analyzes the pooled data using statistical tests. Examples of clinical trial goals include assessing the safety and relative effectiveness of a medication or device: On a specific kind of patient, for example, a patient, diagnosed with Alzheimer's disease At varying dosages, for example, a 10 milligram dose instead of a 5 milligram dose For a new indication Evaluation for improved efficacy in treating a patient's condition as compared to the standard therapy for that condition Evaluation of the study drug or device relative to two or more approved/common interventions for that condition, for example, device A versus device B, or therapy A versus therapy B)While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo.
Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol. The protocol is the trial's "operating manual" and ensures that all researchers perform the trial in the same way on similar subjects and that the data is comparable across all subjects; as a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, psychological therapies, or other interventions. Clinical trials may be required before a national regulatory authority approves marketing of the innovation. To drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket appr
Protein Data Bank
The Protein Data Bank is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data obtained by X-ray crystallography, NMR spectroscopy, or cryo-electron microscopy, submitted by biologists and biochemists from around the world, are accessible on the Internet via the websites of its member organisations; the PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB. The PDB is a key in areas such as structural genomics. Most major scientific journals, 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. Two forces converged to initiate the PDB: 1) a small but growing collection of sets of protein structure data determined by X-ray diffraction.
In 1969, with the sponsorship of Walter Hamilton at the Brookhaven National Laboratory, Edgar Meyer began to write software to store atomic coordinate files in a common format to make them available for geometric and graphical evaluation. By 1971, one of Meyer's programs, SEARCH, enabled researchers to remotely access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the functional beginning of the PDB; the Protein Data Bank was announced in October 1971 in Nature New Biology as a joint venture between Cambridge Crystallographic Data Centre, UK and Brookhaven National Laboratory, USA. Upon Hamilton's death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years. In January 1994, Joel Sussman of Israel's 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, PDBj; the BMRB joined in 2006. Each of the four members of wwPDB can act as deposition, data processing and distribution centers for PDB data; the data processing refers to the fact that annotate each submitted entry. The data are automatically checked for plausibility; the PDB database is updated weekly. The PDB holdings list is updated weekly; as of 17 October 2018, the breakdown of current holdings is as follows: 120,052 structures in the PDB have a structure factor file. 9,734 structures have an NMR restraint file. 3,486 structures in the PDB have a chemical shifts file. 2,531 structures in the PDB have a 3DEM map file deposited in EM Data BankThese data show that most structures are determined by X-ray diffraction, but about 10% of structures are now determined by protein NMR. When using X-ray diffraction, approximations of the coordinates of the atoms of the protein are obtained, whereas estimations of the distances between pairs of atoms of the protein are found through NMR experiments.
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". In the past, the number of structures in the PDB has grown at an exponential rate, passing the 100 registered structures milestone in 1982, the 1,000 in 1993, the 10,000 in 1999, the 100,000 in 2014. 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, an extension of the CIF format started to be phased in.
MmCIF is now the master format for the PDB archive. An XML version of this format, called PDBML, was described in 2005; the structure files can be downloaded in any of these three formats. In fact, individual files are downloaded into graphics packages using web addresses: For PDB format files, use, e.g. http://www.pdb.org/pdb/files/4hhb.pdb.gz or http://pdbe.org/download/4hhb For PDBML files, use, e.g. http://www.pdb.org/pdb/files/4hhb.xml.gz or http://pdbe.org/pdbml/4hhbThe "4hhb" is the PDB identifier. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID; the structure files may be viewed using one of several free and open source computer programs, including Jmol, Pymol, VMD, Rasmol. Other non-free, shareware programs
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, transporting molecules from one location to another. Proteins differ from one another in their sequence of amino acids, dictated by the nucleotide sequence of their genes, which results in protein folding into a specific three-dimensional structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are considered to be proteins and are called peptides, or sometimes oligopeptides; the individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in a protein is defined by the sequence of a gene, encoded in the genetic code.
In general, the genetic code specifies 20 standard amino acids. Shortly after or during synthesis, the residues in a protein are chemically modified by post-translational modification, which alters the physical and chemical properties, stability and the function of the proteins. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors. Proteins can work together to achieve a particular function, they associate to form stable protein complexes. Once formed, proteins only exist for a certain period and are degraded and recycled by the cell's machinery through the process of protein turnover. A protein's lifespan covers a wide range, they can exist for years with an average lifespan of 1 -- 2 days in mammalian cells. Abnormal or misfolded proteins are degraded more either due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in every process within cells.
Many proteins are enzymes that are vital to metabolism. Proteins have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses, cell adhesion, the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized. Digestion breaks the proteins down for use in the metabolism. Proteins may be purified from other cellular components using a variety of techniques such as ultracentrifugation, precipitation and chromatography. Methods used to study protein structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance and mass spectrometry. Most proteins consist of linear polymers built from series of up to 20 different L-α- amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, a variable side chain are bonded.
Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids, have a great variety of chemical structures and properties; the amino acids in a polypeptide chain are linked by peptide bonds. Once linked in the protein chain, an individual amino acid is called a residue, the linked series of carbon and oxygen atoms are known as the main chain or protein backbone; the peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are coplanar. The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone; the end with a free amino group is known as the N-terminus or amino terminus, whereas the end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus.
The words protein and peptide are a little ambiguous and can overlap in meaning. Protein is used to refer to the complete biological molecule in a stable conformation, whereas peptide is reserved for a short amino acid oligomers lacking a stable three-dimensional structure. However, the boundary between the two is not well defined and lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids regardless of length, but implies an absence of a defined conformation. Proteins can interact with many types of molecules, including with other proteins, with lipids, with carboyhydrates, with DNA, it has been estimated. Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, on the order of 50,000 to 1 million. By contrast, eukaryotic cells are larger and thus contain much more pro
Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, a phosphate group; the nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
This information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences; the two strands of DNA are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. DNA was first isolated by Friedrich Miescher in 1869, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings; these are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
A reverse transcriptase is an enzyme used to generate complementary DNA from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by retroviruses to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes, by some non-retroviruses such as the hepatitis B virus, a member of the Hepadnaviridae, which are dsDNA-RT viruses. Retroviral RT has three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H, DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can integrate into the host genome, from which new RNA copies can be made via host-cell transcription; the same sequence of reactions is used in the laboratory to convert RNA to DNA for use in molecular cloning, RNA sequencing, polymerase chain reaction, or genome analysis.
Reverse transcriptases were discovered by Howard Temin at the University of Wisconsin–Madison in RSV virions and independently isolated by David Baltimore in 1970 at MIT from two RNA tumour viruses: R-MLV and again RSV. For their achievements, both shared the 1975 Nobel Prize in Medicine. Well studied reverse transcriptases include: HIV-1 reverse transcriptase from human immunodeficiency virus type 1 has two subunits, which have respective molecular weights of 66 and 51 kDa. M-MLV reverse transcriptase from the Moloney murine leukemia virus is a single 75 kDa monomer. AMV reverse transcriptase from the avian myeloblastosis virus has two subunits, a 63 kDa subunit and a 95 kDa subunit. Telomerase reverse transcriptase; the enzymes are encoded and used by viruses that use reverse transcription as a step in the process of replication. Reverse-transcribing RNA viruses, such as retroviruses, use the enzyme to reverse-transcribe their RNA genomes into DNA, integrated into the host genome and replicated along with it.
Reverse-transcribing DNA viruses, such as the hepadnaviruses, can allow RNA to serve as a template in assembling and making DNA strands. HIV infects humans with the use of this enzyme. Without reverse transcriptase, the viral genome would not be able to incorporate into the host cell, resulting in failure to replicate. Reverse transcriptase creates double-stranded DNA from an RNA template. In virus species with reverse transcriptase lacking DNA-dependent DNA polymerase activity, creation of double-stranded DNA can be done by host-encoded DNA polymerase δ, mistaking the viral DNA-RNA for a primer and synthesizing a double-stranded DNA by similar mechanism as in primer removal, where the newly synthesized DNA displaces the original RNA template; the process of reverse transcription is error-prone, it is during this step that mutations may occur. Such mutations may cause drug resistance. Retroviruses referred to as class VI ssRNA-RT viruses, are RNA reverse-transcribing viruses with a DNA intermediate.
Their genomes consist of two molecules of positive-sense single-stranded RNA with a 5' cap and 3' polyadenylated tail. Examples of retroviruses include the human immunodeficiency virus and the human T-lymphotropic virus. Creation of double-stranded DNA occurs in the cytosol as a series of these steps: Lysyl tRNA acts as a primer and hybridizes to a complementary part of the virus RNA genome called the primer binding site or PBS. Reverse transcriptase adds DNA nucleotides onto the 3' end of the primer, synthesizing DNA complementary to the U5 and R region of the viral RNA. A domain on the reverse transcriptase enzyme called RNAse H degrades the U5 and R regions on the 5’ end of the RNA; the tRNA primer "jumps" to the 3’ end of the viral genome, the newly synthesised DNA strands hybridizes to the complementary R region on the RNA. The complementary DNA added in is further extended; the majority of viral RNA is degraded by RNAse H. Synthesis of the second DNA strand begins; the tRNA primer leaves and a "jump" happens.
The PBS from the second strand hybridizes with the complementary PBS on the first strand. Both strands are extended to form a complete double-stranded DNA copy of the original viral RNA genome, which can be incorporated into the host's genome by the enzyme integrase. Creation of double-stranded DNA involves strand transfer, in which there is a translocation of short DNA product from initial RNA-dependent DNA synthesis to acceptor template regions at the other end of the genome, which are reached and processed by the reverse transcriptase for its DNA-dependent DNA activity. Retroviral RNA is arranged in 5’ terminus to 3’ terminus; the site where the primer is annealed to viral RNA is called the primer-binding site. The RNA 5’end to the PBS site is called U5, the RNA 3’ end to the PBS is called the leader; the tRNA primer is unwound between 14 and 22 nucleotides and forms a base-paired duplex with the viral RNA at PBS. The fact that the PBS is located near the 5’ terminus of viral RNA is unusual because reverse transcriptase synthesize DNA from 3’ end of the primer in the 5’ to 3’ direction.
Therefore, the primer and reverse transcriptase must be relocated to 3’ end of viral RNA. In order to accomplish this reposition, multiple steps and various enzymes including DNA polymerase, ribonuclease H and polynucleotide unwinding are needed; the HIV reverse tr
Enzymes are macromolecular biological catalysts. Enzymes accelerate chemical reactions; the molecules upon which enzymes may act are called substrates and the enzyme converts the substrates into different molecules known as products. All metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps; the study of enzymes is called enzymology and a new field of pseudoenzyme analysis has grown up, recognising that during evolution, some enzymes have lost the ability to carry out biological catalysis, reflected in their amino acid sequences and unusual'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins; the latter are called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction rate 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 otherwise take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, nor do they alter the equilibrium of a reaction. 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, activators are molecules that increase activity. Many therapeutic drugs and poisons are enzyme inhibitors. An enzyme's activity decreases markedly outside its optimal temperature and pH, many enzymes are denatured when exposed to excessive heat, losing their structure and catalytic properties; some enzymes are used commercially, in the synthesis of antibiotics. Some household products use enzymes to speed up chemical reactions: enzymes in biological washing powders break down protein, starch or fat stains on clothes, enzymes in meat tenderizer break down proteins into smaller molecules, making the meat easier to chew.
By the late 17th and early 18th centuries, the digestion of meat by stomach secretions and the conversion of starch to sugars by plant extracts and saliva were known but the mechanisms by which these occurred had not been identified. French chemist Anselme Payen was the first to discover an enzyme, diastase, in 1833. A few decades when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that this fermentation was caused by a vital force contained within the yeast cells called "ferments", which were thought to function only within living organisms, 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, which comes from Greek ἔνζυμον, "leavened" or "in yeast", to describe this process. The word enzyme was used to refer to nonliving substances such as pepsin, 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 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 Buchner's example, enzymes are named according to the reaction they carry out: the suffix -ase is combined with the name of the substrate or to the type of reaction; the biochemical identity of enzymes was still unknown in the early 1900s. Many scientists observed that enzymatic activity was associated with proteins, but others argued that proteins were carriers for the true enzymes and that proteins per se were incapable of catalysis. In 1926, James B. Sumner crystallized it; the conclusion that pure proteins can be enzymes was definitively demonstrated by John Howard Northrop and Wendell Meredith Stanley, who worked on the digestive enzymes pepsin and chymotrypsin.
These three scientists were awarded the 1946 Nobel Prize in Chemistry. The discovery that enzymes could be crystallized allowed their structures to be solved by x-ray crystallography; this was first done for lysozyme, an enzyme found in tears and egg whites that digests the coating of some bacteria. This high-resolution structure of lysozyme marked the beginning of the field of structural biology and the effort to understand how enzymes work at an atomic level of detail. An enzyme's name is derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase. Examples are alcohol dehydrogenase and DNA polymerase. Different enzymes that catalyze the same chemical reaction are called isozymes; the International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the EC numbers. The first number broadly classifies the enzyme based on its mechanism; the top-level classification is: EC 1, Oxidoreductases: catalyze oxidation/reducti