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
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin; the tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules; the result is a polyubiquitin chain, bound by the proteasome, allowing it to degrade the tagged protein. The degradation process yields peptides of about seven to eight amino acids long, which can be further degraded into shorter amino acid sequences and used in synthesizing new proteins. Proteasomes are found inside all eukaryotes and archaea, in some bacteria. In eukaryotes, proteasomes are located both in the cytoplasm.
In structure, the proteasome is a cylindrical complex containing a "core" of four stacked rings forming a central pore. Each ring is composed of seven individual proteins; the inner two rings are made of seven β subunits. These sites are located on the interior surface of the rings, so that the target protein must enter the central pore before it is degraded; the outer two rings each contain seven α subunits whose function is to maintain a "gate" through which proteins enter the barrel. These α subunits are controlled by binding to "cap" structures or regulatory particles that recognize polyubiquitin tags attached to protein substrates and initiate the degradation process; the overall system of ubiquitination and proteasomal degradation is known as the ubiquitin-proteasome system. The proteasomal degradation pathway is essential for many cellular processes, including the cell cycle, the regulation of gene expression, responses to oxidative stress; the importance of proteolytic degradation inside cells and the role of ubiquitin in proteolytic pathways was acknowledged in the award of the 2004 Nobel Prize in Chemistry to Aaron Ciechanover, Avram Hershko and Irwin Rose.
Before the discovery of the ubiquitin proteasome system, protein degradation in cells was thought to rely on lysosomes, membrane-bound organelles with acidic and protease-filled interiors that can degrade and recycle exogenous proteins and aged or damaged organelles. However, work by Joseph Etlinger and Alfred Goldberg in 1977 on ATP-dependent protein degradation in reticulocytes, which lack lysosomes, suggested the presence of a second intracellular degradation mechanism; this was shown in 1978 to be composed of several distinct protein chains, a novelty among proteases at the time. Work on modification of histones led to the identification of an unexpected covalent modification of the histone protein by a bond between a lysine side chain of the histone and the C-terminal glycine residue of ubiquitin, a protein that had no known function, it was discovered that a identified protein associated with proteolytic degradation, known as ATP-dependent proteolysis factor 1, was the same protein as ubiquitin.
The proteolytic activities of this system were isolated as a multi-protein complex called the multi-catalytic proteinase complex by Sherwin Wilk and Marion Orlowski. The ATP-dependent proteolytic complex, responsible for ubiquitin-dependent protein degradation was discovered and was called the 26S proteasome. Much of the early work leading up to the discovery of the ubiquitin proteasome system occurred in the late 1970s and early 1980s at the Technion in the laboratory of Avram Hershko, where Aaron Ciechanover worked as a graduate student. Hershko's year-long sabbatical in the laboratory of Irwin Rose at the Fox Chase Cancer Center provided key conceptual insights, though Rose downplayed his role in the discovery; the three shared the 2004 Nobel Prize in Chemistry for their work in discovering this system. Although electron microscopy data revealing the stacked-ring structure of the proteasome became available in the mid-1980s, the first structure of the proteasome core particle was not solved by X-ray crystallography until 1994.
The proteasome subcomponents are referred to by their Svedberg sedimentation coefficient. The proteasome most used in mammals is the cytosolic 26S proteasome, about 2000 kilodaltons in molecular mass containing one 20S protein subunit and two 19S regulatory cap subunits; the core provides an enclosed cavity in which proteins are degraded. Each end of the core particle associates with a 19S regulatory subunit that contains multiple ATPase active sites and ubiquitin binding sites. An alternative form of regulatory subunit called the 11S particle can associate with the core in the same manner as the 19S particle; the number and diversity of subunits contained in the 20S core particle depends on the organism. All 20S particles consist of four stacked heptameric ring structures that are themselves composed of two different types of subunits; the α subunits are pseudoenzymes homologous to β subunits. They are assembled with their N-termini adjacent to
In humans, the respiratory tract is the part of the anatomy of the respiratory system involved with the process of respiration. Air is breathed in through the mouth. In the nasal cavity, a layer of mucous membrane acts as a filter and traps pollutants and other harmful substances found in the air. Next, air moves into the pharynx, a passage that contains the intersection between the esophagus and the larynx; the opening of the larynx has a special flap of cartilage, the epiglottis, that opens to allow air to pass through but closes to prevent food from moving into the airway. From the larynx, air moves into the trachea and down to the intersection that branches to form the right and left primary bronchi; each of these bronchi branch into secondary bronchi that branch into tertiary bronchi that branch into smaller airways called bronchioles that connect with tiny specialized structures called alveoli that function in gas exchange. The lungs which are located in the thoracic cavity, are protected from physical damage by the rib cage.
At the base of the lungs is a sheet of skeletal muscle called the diaphragm. The diaphragm separates the lungs from intestines; the diaphragm is the main muscle of respiration involved in breathing, is controlled by the sympathetic nervous system. The lungs are encased in a serous membrane that folds in on itself to form the pleurae – a two-layered protective barrier; the inner visceral pleura covers the surface of the lungs, the outer parietal pleura is attached to the inner surface of the thoracic cavity. The pleurae enclose; this fluid is used to decrease the amount of friction. The respiratory tract is divided into lower airways; the upper airways or upper respiratory tract includes the nose and nasal passages, paranasal sinuses, the pharynx, the portion of the larynx above the vocal folds. The lower airways or lower respiratory tract includes the portion of the larynx below the vocal folds, trachea and bronchioles; the lungs can be included in the lower respiratory tract or as separate entity and include the respiratory bronchioles, alveolar ducts, alveolar sacs, alveoli.
The respiratory tract can be divided into a conducting zone and a respiratory zone, based on the distinction of transporting gases or exchanging them. The conducting zone includes structures outside of the lungs – the nose, pharynx and trachea, structures inside the lungs – the bronchi and terminal bronchioles; the conduction zone conducts air breathed in, filtered and moistened, into the lungs. It represents the 1st through the 16th division of the respiratory tract; the conducting zone is most of the respiratory tract that conducts gases into and out of the lungs, but excludes the respiratory zone that exchanges gases. The conducting zone functions to offer a low resistance pathway for airflow, it provides a major defense role in its filtering abilities. The respiratory zone includes the respiratory bronchioles, alveolar ducts and alveoli, is the site of oxygen and carbon dioxide exchange with the blood; the respiratory bronchioles and the alveolar ducts are responsible for 10% of the gas exchange.
The alveoli are responsible for the other 90%. The respiratory zone represents the 16th through the 23rd division of the respiratory tract. From the bronchi, the dividing tubes become progressively smaller with an estimated 20 to 23 divisions before ending at an alveolus; the upper respiratory tract, can refer to the parts of the respiratory system lying above the sternal angle, above the vocal folds, or above the cricoid cartilage. The larynx is sometimes included in both lower airways; the larynx is called the voice box and has the associated cartilage that produces sound. The tract consists of the nasal cavity and paranasal sinuses, the pharynx and sometimes includes the larynx; the lower respiratory tract or lower airway is derived from the developing foregut and consists of the trachea, bronchi and lungs. It sometimes includes the larynx; the lower respiratory tract is called the respiratory tree or tracheobronchial tree, to describe the branching structure of airways supplying air to the lungs, includes the trachea and bronchioles.
Trachea main bronchus lobar bronchus segmental bronchus subsegmental bronchus conducting bronchiole terminal bronchiole respiratory bronchiole alveolar duct alveolar sac alveolusAt each division point or generation, one airway branches into two or more smaller airways. The human respiratory tree may consist on average of 23 generations, while the respiratory tree of the mouse has up to 13 generations. Proximal divisions function to transmit air to the lower airways. Divisions including the respiratory bronchiole, alveolar ducts and alveoli, are specialized for gas exchange; the trachea is the largest tube in the respiratory tract and consists of tracheal rings of hyaline cartilage. It branches off into a left and a right main bronchus; the bronchi branch off into smaller sections inside the lungs, called bronchioles. These bronchioles give rise to the air sacs in the lungs called the alveoli; the lungs are the largest organs in the lower respiratory tract. The lungs are suspended within the pleural cavity of the thorax.
The pleurae are two thin membranes, one
Chemokines are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells. Cytokine proteins are classified as chemokines according to structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all 8-10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape; these proteins have been known under several other names including the SIS family of cytokines, SIG family of cytokines, SCY family of cytokines, Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates, some viruses and some bacteria, but none have been described for other invertebrates.
Chemokines have been classified into four main subfamilies: CXC, CC, CX3C and XC. All of these proteins exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors, that are selectively found on the surfaces of their target cells; the major role of chemokines is to act as a chemoattractant to guide the migration of cells. Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine; some chemokines control cells of the immune system during processes of immune surveillance, such as directing lymphocytes to the lymph nodes so they can screen for invasion of pathogens by interacting with antigen-presenting cells residing in these tissues. These are known as homeostatic chemokines and are produced and secreted without any need to stimulate their source cell; some chemokines have roles in development. Other chemokines are inflammatory and are released from a wide variety of cells in response to bacterial infection and agents that cause physical damage such as silica or the urate crystals that occur in gout.
Their release is stimulated by pro-inflammatory cytokines such as interleukin 1. Inflammatory chemokines function as chemoattractants for leukocytes, recruiting monocytes and other effector cells from the blood to sites of infection or tissue damage. Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing, they are released by many different cell types and serve to guide cells of both innate immune system and adaptive immune system. Chemokines are functionally divided into two groups: Homeostatic: are constitutively produced in certain tissues and are responsible for basal leukocyte migration; these include: CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13. This classification is not strict. Inflammatory: these are formed under pathological conditions and participate in the inflammatory response attracting immune cells to the site of inflammation. Examples are: CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, CXCL10; the main function of chemokines is to manage the migration of leukocytes in the respective anatomical locations in inflammatory and homeostatic processes.
Basal: homeostatic chemokines are basal produced in the thymus and lymphoid tissues. Their homeostatic function in homing is best exemplified by the chemokines CCL19 and CCL21 and their receptor CCR7. Using these ligands is possible routing antigen-presenting cells to lymph nodes during the adaptive immune response. Among other homeostatic chemokine receptors include: CCR9, CCR10, CXCR5, which are important as part of the cell addresses for tissue-specific homing of leukocytes. CCR9 supports the migration of leukocytes into the intestine, CCR10 to the skin and CXCR5 supports the migration of B-cell to follicles of lymph nodes; as well CXCL12 constitutively produced in the bone marrow promotes proliferation of progenitor B cells in the bone marrow microenvironment. Inflammatory: inflammatory chemokines are produced in high concentrations during infection or injury and determine the migration of inflammatory leukocytes into the damaged area. Typical inflammatory chemokines include: CCL2, CCL3 and CCL5, CXCL1, CXCL2 and CXCL8.
A typical example is CXCL-8. In contrast to the homeostatic chemokine receptors, there is significant promiscuity associated with binding receptor and inflammatory chemokines; this complicates research on receptor-specific therapeutics in this area. Monocytes / macrophages: the key chemokines that attract these cells to the site of inflammation include: CCL2, CCL3, CCL5, CCL7, CCL8, CCL13, CCL17 and CCL22. T-lymphocytes: the four key chemokines that are involved in the recruitment of T lymphocytes to the site of inflammation are: CCL2, CCL1, CCL22 and CCL17. Furthermore, CXCR3 expression by T-cells is induced following T-cell activation and activated T-cells are attracted to sites of inflammation where the IFN-y inducible chemokines CXCL9, CXCL10 and CXCL11 are secreted. Mast cells: on their surface express several receptors for chemokines: CCR1, CCR2, CCR3, CCR4, CCR5, CXCR2, CXCR4. Ligands of
In cell biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are 500 nm in diameter when mature. Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates from the receptor, the receptor can be recycled to the cell surface.
The LDL is delivered to lysosomes for processing. LDL dissociates because of the acidified environment of the early endosome, generated by a vacuolar membrane proton pump V-ATPase. On the other hand, EGF and the EGF receptor have a pH-resistant bond that persists until it is delivered to lysosomes for their degradation; the mannose 6-phosphate receptor carries ligands from the Golgi destined for the lysosome by a similar mechanism. There are three different types of endosomes: early endosomes, late endosomes, recycling endosomes, they are distinguished by the time it takes for endocytosed material to reach them, by markers such as rabs. They have different morphology. Once endocytic vesicles have uncoated, they fuse with early endosomes. Early endosomes mature into late endosomes before fusing with lysosomes. Early endosomes mature in several ways to form late endosomes, they become acidic through the activity of the V-ATPase. Many molecules that are recycled are removed by concentration in the tubular regions of early endosomes.
Loss of these tubules to recycling pathways means that late endosomes lack tubules. They increase in size due to the homotypic fusion of early endosomes into larger vesicles. Molecules are sorted into smaller vesicles that bud from the perimeter membrane into the endosome lumen, forming lumenal vesicles. Removal of recycling molecules such as transferrin receptors and mannose 6-phosphate receptors continues during this period via budding of vesicles out of endosomes; the endosomes lose RAB5A and acquire RAB7A, making them competent for fusion with lysosomes. Fusion of late endosomes with lysosomes has been shown to result in the formation of a'hybrid' compartment, with characteristics intermediate of the two source compartments. For example, lysosomes are more dense than late endosomes, the hybrids have an intermediate density. Lysosomes reform by recondensation to their normal, higher density. However, before this happens, more late endosomes may fuse with the hybrid; some material recycles to the plasma membrane directly from early endosomes, but most traffics via recycling endosomes.
Early endosomes consist of a dynamic tubular-vesicular network. Markers include RAB5A and RAB4, Transferrin and its receptor and EEA1. Late endosomes known as MVBs, are spherical, lack tubules, contain many close-packed lumenal vesicles. Markers include RAB7, RAB9, mannose 6-phosphate receptors. Recycling endosomes are concentrated at the microtubule organizing center and consist of a tubular network. Marker. More subtypes exist in specialized cells such as polarized macrophages. Phagosomes and autophagosomes mature in a manner similar to endosomes, may require fusion with normal endosomes for their maturation; some intracellular pathogens subvert this process, by preventing RAB7 acquisition. Late endosomes/MVBs are sometimes called endocytic carrier vesicles, but this term was used to describe vesicles that bud from early endosomes and fuse with late endosomes. However, several observations have now demonstrated that it is more that transport between these two compartments occurs by a maturation process, rather than vesicle transport.
Another unique identifying feature that differs between the various classes of endosomes is the lipid composition in their membranes. Phosphatidyl inositol phosphates, one of the most important lipid signaling molecules, is found to differ as the endosomes mature from early to late. PIP2 is present on plasma membranes, PIP on early endosomes, PIP2 on late endosomes and PIP on the trans Golgi network; these lipids on the surface of the endosomes help in the specific recruitment of proteins from the cytosol, thus providing them an identity. The inter-conversion of these lipids is a result of the concerted action of phosphoinositide kinases and phosphatases that are strategically localized There are three main compartments that have pathways that connect with endosomes. More pathways exist in specialized cells, such as polarized cells. For example, in epithelial cells, a special process called transcytosis allows some materials to enter one side of a cell and exit from the opposite side. In some circumstances, late endosomes/MVBs fuse with the plasma membrane instead of with lysosomes, releasing the lumenal vesicles, now called exosomes, into the extracellular medium.
There is no consensus as to
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
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax and rabies; the institute was founded on June 4, 1887, inaugurated on November 14, 1888. For over a century, the Institut Pasteur has been at the forefront of the battle against infectious disease; this worldwide biomedical research organization based in Paris was the first to isolate HIV, the virus that causes AIDS, in 1983. Over the years, it has been responsible for breakthrough discoveries that have enabled medical science to control such virulent diseases as diphtheria, tuberculosis, influenza, yellow fever, plague. Since 1908, eight Institut Pasteur scientists have been awarded the Nobel Prize for medicine and physiology, the 2008 Nobel Prize in Physiology or Medicine was shared between two Pasteur scientists.
The Institut Pasteur was founded in 1887 by Louis Pasteur, the famous French chemist and microbiologist. He was committed both to its practical applications; as soon as his institute was created, Pasteur brought together scientists with various specialties. The first five departments were directed by two normaliens: Émile Duclaux and Charles Chamberland, as well as a biologist, Ilya Ilyich Mechnikov and two physicians, Jacques-Joseph Grancher and Emile Roux. One year after the inauguration of the Institut Pasteur, Roux set up the first course of microbiology taught in the world entitled Cours de Microbie Technique. Pasteur's successors have sustained this tradition, it is reflected in the Institut Pasteur's unique history of accomplishment: Emile Roux and Alexandre Yersin discovered the mechanism of action of Corynebacterium diphtheriae and how to treat diphtheria with antitoxins. Luc Montagnier, Françoise Barré-Sinoussi and colleagues discovered the two HIV viruses that cause AIDS, in 1983 and 1985, was honored by the 2008 Nobel Prize in Physiology or MedicineThe biggest mistake by the Institute was ignoring a dissertation by Ernest Duchesne on the use of Penicillium glaucum to cure infections in 1897.
The early exploitation of his discovery might have saved millions of lives in World War I. A new age of preventive medicine in France was made possible by such developments from the Institut Pasteur as vaccines for tuberculosis, tetanus, yellow fever and hepatitis B; the discovery and use of sulfonamides in treating infections was another breakthrough. Some researchers won fame by discovering antitoxins and Daniel Bovet received the 1957 Nobel Prize for his discoveries on synthetic anti-histamines and curarizing compounds. Since World War II, Pasteur researchers have focused on molecular biology, their achievements were recognized in 1965, when the Nobel Prize was shared by François Jacob, Jacques Monod and André Lwoff for their work on the regulation of viruses. In 1985, the first human vaccine obtained by genetic engineering from animal cells, the vaccine against hepatitis B, was developed by Pierre Tiollais and collaborators. Although the center against rabies, directed by Jacques-Joseph Grancher and Émile Roux was more than functional, it became so overcrowded that it became necessary to build a structure that Pasteur had been calling with the name “Institute Pasteur” long before it was built.
Since Pasteur could not, for health reasons, do it himself, he delegated the task of the project and of creating the new building, situated on rue Dutot, to two of his most trusted colleagues and Emile Duclaux. From the beginning the Institute experienced some economical difficulties that it was able to overcome thanks to the help of the government, some foreign rulers and Madame Boucicaut, but