Rhodopsin-like receptors are a family of proteins that comprise the largest group of G protein-coupled receptors. G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions, they show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. GPCRs are described as "superfamily" because they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence; the known superfamily members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, the metabotropic glutamate receptor family. There is a specialised database for GPCRs; the rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormones, neurotransmitters, light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding proteins.
Although their activating ligands vary in structure and character, the amino acid sequences of the receptors are similar and are believed to adopt a common structural framework comprising 7 transmembrane helices. Rhodopsin-like GPCRs have been classified into the following 19 subgroups based on a phylogenetic analysis. Chemokine receptor InterPro: IPR000355 Chemokine receptor 1 Chemokine receptor 2 Chemokine receptor 3 Chemokine receptor 4 Chemokine receptor 5 Chemokine receptor 8 Chemokine receptor-like 2 chemokine receptor 1 InterPro: IPR005393 chemokine receptor 1 InterPro: IPR005387 GPR137B Chemokine receptor InterPro: IPR000355 Chemokine receptor-like 1 Chemokine receptor 6 Chemokine receptor 7 Chemokine receptor 9 Chemokine receptor 10 CXC chemokine receptors InterPro: IPR001053 Chemokine receptor 3 Chemokine receptor 4 Chemokine receptor 5 Chemokine receptor 6 Chemokine receptor 7 InterPro: IPR001416 Interleukin-8 InterPro: IPR000174 IL8R-α IL8R-β Adrenomedullin receptor Duffy blood group, chemokine receptor G Protein-coupled Receptor 30 Angiotensin II receptor InterPro: IPR000248 Angiotensin II receptor, type 1 Angiotensin II receptor, type 2 Apelin receptor InterPro: IPR003904 Bradykinin receptor InterPro: IPR000496 Bradykinin receptor B1 Bradykinin receptor B2 GPR15 GPR25 Opioid receptor InterPro: IPR001418 delta Opioid receptor kappa Opioid receptor mu Opioid receptor Nociceptin receptor Somatostatin receptor InterPro: IPR000586 Somatostatin receptor 1 Somatostatin receptor 2 Somatostatin receptor 3 Somatostatin receptor 4 Somatostatin receptor 5 GPCR neuropeptide receptor InterPro: IPR009150 Neuropeptides B/W receptor 1 Neuropeptides B/W receptor 2 GPR1 orphan receptor InterPro: IPR002275 Galanin receptor InterPro: IPR000405 Galanin receptor 1 Galanin receptor 2 Galanin receptor 3 Cysteinyl leukotriene receptor InterPro: IPR004071 Cysteinyl leukotriene receptor 1 Cysteinyl leukotriene receptor 2 Leukotriene B4 receptor InterPro: IPR003981 Leukotriene B4 receptor Leukotriene B4 receptor 2 Relaxin receptor InterPro: IPR008112 Relaxin/insulin-like family peptide receptor 1 Relaxin/insulin-like family peptide receptor 2 Relaxin/insulin-like family peptide receptor 3 Relaxin/insulin-like family peptide receptor 4 KiSS1-derived peptide receptor InterPro: IPR008103 Melanin-concentrating hormone receptor 1 InterPro: IPR008361 Urotensin-II receptor InterPro: IPR000670 Cholecystokinin receptor InterPro: IPR009126 Cholecystokinin A receptor Cholecystokinin B receptor Neuropeptide FF receptor InterPro: IPR005395 Neuropeptide FF receptor 1 Neuropeptide FF receptor 2 Orexin receptor InterPro: IPR000204 Hypocretin receptor 1 Hypocretin receptor 2 Vasopressin receptor InterPro: IPR001817 Arginine vasopressin receptor 1A Arginine vasopressin receptor 1B Arginine vasopressin receptor 2 Oxytocin receptor Gonadotrophin releasing hormone receptor InterPro: IPR001658 Pyroglutamylated RFamide peptide receptor GPR22 GPR176 Bombesin receptor InterPro: IPR001556 Bombesin-like receptor 3 Neuromedin B receptor Gastrin-releasing peptide receptor Endothelin receptor InterPro: IPR000499 Endothelin receptor type A Endothelin receptor type B GPR37 InterPro: IPR003909 Neuromedin U receptor InterPro: IPR005390 Neuromedin U receptor 1 Neuromedin U receptor 2 Neurotensin receptor InterPro: IPR003984 Neurotensin receptor 1 Neurotensin receptor 2 Thyrotropin-releasing hormone receptor (TRHR, TRF
Chromosome 3 is one of the 23 pairs of chromosomes in humans. People have two copies of this chromosome. Chromosome 3 spans 200 million base pairs and represents about 6.5 percent of the total DNA in cells. The following are some of the gene count estimates of human chromosome 3; because researchers use different approaches to genome annotation their predictions of the number of genes on each chromosome varies. Among various projects, the collaborative consensus coding sequence project takes an conservative strategy. So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes; the following is a partial list of genes on human chromosome 3. For complete list, see the link in the infobox on the right. Partial list of the genes located on p-arm of human chromosome 3: Partial list of the genes located on q-arm of human chromosome 3: The following diseases and disorders are some of those related to genes on chromosome 3: National Institutes of Health. "Chromosome 3".
Genetics Home Reference. Retrieved 2017-05-06. "Chromosome 3". Human Genome Project Information Archive 1990–2003. Retrieved 2017-05-06
Smooth muscle is an involuntary non-striated muscle. It is divided into two subgroups. Within single-unit cells, the whole bundle or sheet contracts as a syncytium. Smooth muscle cells are found in the walls of hollow organs, including the stomach, urinary bladder and uterus, in the walls of passageways, such as the arteries and veins of the circulatory system, the tracts of the respiratory and reproductive systems; these cells are present in the eyes and are able to change the size of the iris and alter the shape of the lens. In the skin, smooth muscle cells cause hair to stand erect in response to cold fear. Most smooth muscle is of the single-unit variety, that is, either the whole muscle contracts or the whole muscle relaxes, but there is multiunit smooth muscle in the trachea, the large elastic arteries, the iris of the eye. Single unit smooth muscle, however, is most common and lines blood vessels, the urinary tract, the digestive tract. However, the terms single- and multi-unit smooth muscle represents an oversimplification.
This is due to the fact that smooth muscles for the most part are controlled and influenced by a combination of different neural elements. In addition, it has been observed that most of the time there will be some cell to cell communication and activators/ inhibitors produced locally; this leads to a somewhat coordinated response in multiunit smooth muscle. Smooth muscle is fundamentally different from skeletal muscle and cardiac muscle in terms of structure, regulation of contraction, excitation-contraction coupling. Smooth muscle cells known as myocytes, have a fusiform shape and, like striated muscle, can tense and relax. However, smooth muscle tissue tends to demonstrate greater elasticity and function within a larger length-tension curve than striated muscle; this ability to stretch and still maintain contractility is important in organs like the intestines and urinary bladder. In the relaxed state, each cell is 20 -- 500 micrometers in length. A substantial portion of the volume of the cytoplasm of smooth muscle cells are taken up by the molecules myosin and actin, which together have the capability to contract, through a chain of tensile structures, make the entire smooth muscle tissue contract with them.
Myosin is class II in smooth muscle. Myosin II contains two heavy chains which constitute the tail domains; each of these heavy chains contains the N-terminal head domain, while the C-terminal tails take on a coiled-coil morphology, holding the two heavy chains together. Thus, myosin II has two heads. In smooth muscle, there is a single gene that codes for the heavy chains myosin II, but there are splice variants of this gene that result in four distinct isoforms. Smooth muscle may contain MHC, not involved in contraction, that can arise from multiple genes. Myosin II contains 4 light chains, resulting in 2 per head, weighing 20 and 17 kDa; these bind the heavy chains in the "neck" region between the head and tail. The MLC20 is known as the regulatory light chain and participates in muscle contraction. Two MLC20 isoforms are found in smooth muscle, they are encoded by different genes, but only one isoform participates in contraction; the MLC17 is known as the essential light chain. Its exact function is unclear, but it's believed that it contributes to the structural stability of the myosin head along with MLC20.
Two variants of MLC17 exist as a result of alternative splicing at the MLC17 gene. Different combinations of heavy and light chains allow for up to hundreds of different types of myosin structures, but it is unlikely that more than a few such combinations are used or permitted within a specific smooth muscle bed. In the uterus, a shift in myosin expression has been hypothesized to avail for changes in the directions of uterine contractions that are seen during the menstrual cycle; the thin filaments that form part of the contractile machinery are predominantly composed of α- and γ-actin. Smooth muscle α-actin is the predominant isoform within smooth muscle. There are lots of actin that does not take part in contraction, but that polymerizes just below the plasma membrane in the presence of a contractile stimulant and may thereby assist in mechanical tension. Alpha actin is expressed as distinct genetic isoforms such as smooth muscle, cardiac muscle and skeletal muscle specific isoforms of alpha actin.
The ratio of actin to myosin is between 10:1 in smooth muscle. Conversely, from a mass ratio standpoint, myosin is the dominant protein in striated skeletal muscle with the actin to myosin ratio falling in the 1:2 to 1:3 range. A typical value for healthy young adults is 1:2.2.. Tropomyosin is present in smooth muscle, spanning seven actin monomers and is laid out end to end over the entire length of the thin filaments. In striated muscle, tropomyosin serves to block actin–myosin interactions until calcium is present, but in smooth muscle, its function is unknown. Calponin molecules may exist in equal number as actin, has been proposed to be a load-bearing protein. Caldesmon has been suggested to be involved in tethering actin and tropomyosin, thereby enhance the ability of smooth muscle to maintain tension. All three of these proteins may have a role in inhibiting the ATPase activity of the m
G protein-coupled receptor
G protein-coupled receptors known as seven--transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, G protein–linked receptors, constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, animals; the ligands that bind and activate these receptors include light-sensitive compounds, pheromones and neurotransmitters, vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, are the target of 34% of all modern medicinal drugs. There are two principal signal transduction pathways involving the G protein-coupled receptors: the cAMP signal pathway and the phosphatidylinositol signal pathway.
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor. The GPCR can activate an associated G protein by exchanging the GDP bound to the G protein for a GTP; the G protein's α subunit, together with the bound GTP, can dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type. GPCRs are an important drug target and 34% of all Food and Drug Administration approved drugs target 108 members of this family; the global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work, "crucial for understanding how G protein-coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling; as of 2012, two of the top ten global best-selling drugs act by targeting G protein-coupled receptors.
The exact size of the GPCR superfamily is unknown, but at least 810 different human genes have been predicted to code for them from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes with no detectable shared sequence homology between classes; the largest class by far is class A. Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction; the large rhodopsin A group has been further subdivided into 19 subgroups. According to the classical A-F system, GPCRs can be grouped into 6 classes based on sequence homology and functional similarity: Class A Class B Class C Class D Class E Class F More an alternative classification system called GRAFS has been proposed for vertebrate GPCRs.
They correspond to classical classes C, A, B2, F, B. An early study based on available DNA sequence suggested that the human genome encodes 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, other endogenous ligands. 150 of the GPCRs found in the human genome have unknown functions. Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach. GPCRs are involved in a wide variety of physiological processes; some examples of their physiological roles include: The visual sense: The opsins evolved from early GPCRs over 650 million years ago, use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal to all-trans-retinal for this purpose; the gustatory sense: GPCRs in taste cells mediate release of gustducin in response to bitter-, umami- and sweet-tasting substances.
The sense of smell: Receptors of the olfactory epithelium bind odorants and pheromones Behavioral and mood regulation: Receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, GABA, glutamate Regulation of immune system activity and inflammation: Chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system. GPCRs are involved in immune-modulation and directly involved in suppression of TLR-induced immune responses from T cells. Autonomic nervous system transmission: Both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, digestive processes Cell density sensing: A novel GPCR role in regulating cell density sensing. Homeostasis modulation. Involved in growth and metastasis of some types of tumors. Used in the endocrine syste
A chromosome is a deoxyribonucleic acid molecule with part or all of the genetic material of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle. Chromosomes are visible under a light microscope only when the cell is undergoing the metaphase of cell division. Before this happens, every chromosome is copied once, the copy is joined to the original by a centromere, resulting either in an X-shaped structure if the centromere is located in the middle of the chromosome or a two-arm structure if the centromere is located near one of the ends; the original chromosome and the copy are now called sister chromatids. During metaphase the X-shape structure is called a metaphase chromosome. In this condensed form chromosomes are easiest to distinguish and study. In animal cells, chromosomes reach their highest compaction level in anaphase during chromosome segregation.
Chromosomal recombination during meiosis and subsequent sexual reproduction play a significant role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe; this will make the cell initiate apoptosis leading to its own death, but sometimes mutations in the cell hamper this process and thus cause progression of cancer. Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation; the word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, introduced by Walther Flemming; some of the early karyological terms have become outdated.
For example and Chromosom, both ascribe color to a non-colored state. The German scientists Schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now familiar as chromosomes. In a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity, it is the second of these principles, so original. Wilhelm Roux suggested. Boveri was able to confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of Gregor Mendel's earlier work, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Nettie Stevens, Walter Sutton and Theophilus Painter were all influenced by Boveri. In his famous textbook The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton by naming the chromosome theory of inheritance the Boveri–Sutton chromosome theory.
Ernst Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T. H. Morgan, all of a rather dogmatic turn of mind. Complete proof came from chromosome maps in Morgan's own lab; the number of human chromosomes was published in 1923 by Theophilus Painter. By inspection through the microscope, he counted 24 pairs, his error was copied by others and it was not until 1956 that the true number, 46, was determined by Indonesia-born cytogeneticist Joe Hin Tjio. The prokaryotes – bacteria and archaea – have a single circular chromosome, but many variations exist; the chromosomes of most bacteria, which some authors prefer to call genophores, can range in size from only 130,000 base pairs in the endosymbiotic bacteria Candidatus Hodgkinia cicadicola and Candidatus Tremblaya princeps, to more than 14,000,000 base pairs in the soil-dwelling bacterium Sorangium cellulosum. Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome.
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria have a one-point from which replication starts, whereas some archaea contain multiple replication origins; the genes in prokaryotes are organized in operons, do not contain introns, unlike eukaryotes. Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid; the nucleoid occupies a defined region of the bacterial cell. This structure is, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome. In archaea, the DNA in chromosomes is more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes. Certain bacteria contain plasmids or other extrachromosomal DNA; these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. In prokaryotes and viruses, the DNA is densely packed and organized.
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate, a phospholipid, located in the plasma membrane, by phospholipase C. Together with diacylglycerol, IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, a calcium channel located in the endoplasmic reticulum; when IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals. IP3 is an organic molecule with a molecular mass of 420.10 g/mol. Its empirical formula is C6H15O15P3, it is composed of an inositol ring with three phosphate groups bound at the 1, 4, 5 carbon positions, three hydroxyl groups bound at positions 2, 3, 6. Phosphate groups can exist in three different forms depending on a solution's pH.
Phosphorus atoms can bind three oxygen atoms with single bonds and a fourth oxygen atom using a double/dative bond. The pH of the solution, thus the form of the phosphate group determines its ability to bind to other molecules; the binding of phosphate groups to the inositol ring is accomplished by phosphor-ester binding. This bond involves combining a hydroxyl group from the inositol ring and a free phosphate group through a dehydration reaction. Considering that the average physiological pH is 7.4, the main form of the phosphate groups bound to the inositol ring in vivo is PO42−. This gives IP3 a net negative charge, important in allowing it to dock to its receptor, through binding of the phosphate groups to positively charged residues on the receptor. IP3 has three hydrogen bond donors in the form of its three hydroxyl groups; the hydroxyl group on the 6th carbon atom in the inositol ring is involved in IP3 docking. The docking of IP3 to its receptor, called the inositol trisphosphate receptor, was first studied using deletion mutagenesis in the early 1990s.
Studies focused on the N-terminus side of the IP3 receptor. In 1997 researchers localized the region of the IP3 receptor involved with binding of IP3 to between amino acid residues 226 and 578 in 1997. Considering that IP3 is a negatively charged molecule, positively charged amino acids such as arginine and lysine were believed to be involved. Two arginine residues at position 265 and 511 and one lysine residue at position 508 were found to be key in IP3 docking. Using a modified form of IP3, it was discovered that all three phosphate groups interact with the receptor, but not equally. Phosphates at the 4th and 5th positions interact more extensively than the phosphate at the 1st position and the hydroxyl group at the 6th position of the inositol ring; the discovery that a hormone can influence phosphoinositide metabolism was made by Mabel R. Hokin and her husband Lowell E. Hokin in 1953, when they discovered that radioactive 32P phosphate was incorporated into the phosphatidylinositol of pancreas slices when stimulated with acetylcholine.
Up until phospholipids were believed to be innate structures only used by cells as building blocks for construction of the plasma membrane. Over the next 20 years, little was discovered about the importance of PIP2 metabolism in terms of cell signaling, until the mid-1970s when Robert H. Michell hypothesized a connection between the catabolism of PIP2 and increases in intracellular calcium levels, he hypothesized that receptor-activated hydrolysis of PIP2 produced a molecule that caused increases in intracellular calcium mobilization. This idea was researched extensively by Michell and his colleagues, who in 1981 were able to show that PIP2 is hydrolyzed into DAG and IP3 by a unknown phosphodiesterase. In 1984 it was discovered that IP3 acts as a secondary messenger, capable of traveling through the cytoplasm to the endoplasmic reticulum, where it stimulates the release of calcium into the cytoplasm. Further research provided valuable information on the IP3 pathway, such as the discovery in 1986 that one of the many roles of the calcium released by IP3 is to work with DAG to activate protein kinase C.
It was discovered in 1989 that phospholipase C is the phosphodiesterase responsible for hydrolyzing PIP2 into DAG and IP3. Today the IP3 signaling pathway is well mapped out, is known to be important in regulating a variety of calcium-dependent cell signaling pathways. Increases in the intracellular Ca2+ concentrations are a result of IP3 activation; when a ligand binds to a G protein-coupled receptor, coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG. If a receptor tyrosine kinase is involved in activating the pathway, the isozyme PLC-γ has tyrosine residues that can become phosphorylated upon activation of an RTK, this will activate PLC-γ and allow it to cleave PIP2 into DAG and IP3; this occurs in cells that are capable of responding to growth factors such as insulin, because the growth factors are the ligands responsible for activating the RTK. IP3 (also abbreviated InsP3 is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, or the sarcoplasmic reticulum in the case of muscle cells, once it has been produced by the action of PLC.
Once at the ER, IP3 is able to bind to the IInsP3 receptor InsP3R on a ligand-gated Ca2+ channel, found on the surface of the ER. The binding of IP3 to InsP3R triggers the opening of the Ca2+ channel, thus release of Ca2+ in
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