2YDQ
25-458: 10724 76055 ENSG00000198408 ENSMUSG00000025220 O60502 Q9EQQ9 NM_001142434 NM_012215 NM_023799 NP_001135906 NP_036347 NP_076288 Protein O -GlcNAcase ( EC 3.2.1.169 , OGA, glycoside hydrolase O -GlcNAcase, O -GlcNAcase, BtGH84, O -GlcNAc hydrolase) is an enzyme with systematic name (protein)-3- O -( N -acetyl- D -glucosaminyl)- L -serine/threonine N -acetylglucosaminyl hydrolase . OGA
50-472: A halogen-based oxidising agent (e.g. NBS , or iodine ); this potentially proceeds via an imidoyl halide . The method has been shown to be effective for a wide range of aromatic and aliphatic aldehydes however electron rich aromatic R groups, such as phenols , are unsuitable as they preferentially undergo rapid electrophilic aromatic halogenation with the oxidising agent. The use of catalytic amounts of ZnCl 2 to generate oxazolines from nitriles
75-623: A progressively finer classification of the enzyme. Preliminary EC numbers exist and have an 'n' as part of the fourth (serial) digit (e.g. EC 3.5.1.n3). For example, the tripeptide aminopeptidases have the code "EC 3.4.11.4", whose components indicate the following groups of enzymes: NB:The enzyme classification number is different from the 'FORMAT NUMBER' Oxidation /reduction reactions; transfer of H and O atoms or electrons from one substance to another Similarity between enzymatic reactions can be calculated by using bond changes, reaction centres or substructure metrics (formerly EC-BLAST], now
100-572: A pseudo histone-acetyl transferase domain, primarily resides in the cytoplasm and the nucleus. The short isoform S-OGA, which only exhibit the glycoside hydrolase domain, was initially described as residing within the nucleus. However, more recent work showed that S-OGA is located in mitochondria and regulates reactive oxygen production in this organelle. Another isoform, resulting from proteolytic cleavage of L-OGA, has also been described. All three isoforms exhibit glycoside hydrolase activity. Protein O -GlcNAcases belong to glycoside hydrolase family 84 of
125-421: A putative acetyltransferase, eukaryotic translation elongation factor-1γ, and the 11-1 polypeptide. O -GlcNAcylation is a form of glycosylation , the site-specific enzymatic addition of saccharides to proteins and lipids. This form of glycosylation is with O -linked β- N -acetylglucosamine or β- O -linked 2-acetamido-2-deoxy- D -glycopyranose ( O -GlcNAc). In this form, a single sugar (β- N -acetylglucosamine)
150-421: Is a numerical classification scheme for enzymes , based on the chemical reactions they catalyze . As a system of enzyme nomenclature , every EC number is associated with a recommended name for the corresponding enzyme-catalyzed reaction. EC numbers do not specify enzymes but enzyme-catalyzed reactions. If different enzymes (for instance from different organisms) catalyze the same reaction, then they receive
175-485: Is added to serine and threonine residues of nuclear or cytoplasmic proteins. Two conserved enzymes control this glycosylation of serine and threonine: O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA). While OGT catalyzes the addition of O -GlcNAc to serine and threonine, OGA catalyzes the hydrolytic cleavage of O -GlcNAc from post-transitionally modified proteins. OGA is a member of the family of hexosaminidases . However, unlike lysosomal hexosaminidases, OGA activity
200-407: Is commonly used to generate the acid chloride in situ, care being taken to maintain anhydrous conditions, as oxazolines can be ring-opened by chloride if the imine becomes protonated. The reaction is typically performed at room temperature. If reagents milder than SOCl 2 are required, oxalyl chloride can be used. Aminomethyl propanol is a popular precursor amino alcohol. Modification of
225-444: Is encoded by the OGA gene. This enzyme catalyses the removal of the O -GlcNAc post-translational modification in the following chemical reaction : Other names include: The human OGA gene is capable of producing two different transcripts, each capable of encoding a different OGA isoform. The long isoform L-OGA, a bifunctional enzyme that possess a glycoside hydrolase activity and
250-442: Is targeted by inhibitors such as Thiamet-G in order to prevent O -GlcNAc from being removed from tau, which assists in preventing tau from becoming phosphorylated. X-ray structures are available for a range of O -GlcNAcase proteins. The X-ray structure of human O -GlcNAcase in complex with Thiamet-G identified the structural basis of enzyme inhibition. Enzyme Commission number The Enzyme Commission number ( EC number )
275-447: Is the highest at neutral pH (approximately 7) and it localizes mainly to the cytosol. OGA and OGT are synthesized from two conserved genes and are expressed throughout the human body with high levels in the brain and pancreas. The products of O -GlcNAc and the process itself plays a role in embryonic development, brain activity, hormone production, and a myriad of other activities. Over 600 proteins are targets for O -GlcNAcylation. While
SECTION 10
#1733085471046300-612: The Appel reaction allows for the synthesis of oxazoline rings. This method proceeds under relatively mild conditions, however, owing to the large amounts of triphenylphosphine oxide produced, is not ideal for large-scale reactions. The use of this method is becoming less common, due to carbon tetrachloride being restricted under the Montreal protocol . The cyclisation of an amino alcohol and an aldehyde produces an intermediate oxazolidine which can be converted to an oxazoline by treatment with
325-562: The EMBL-EBI Enzyme Portal). Before the development of the EC number system, enzymes were named in an arbitrary fashion, and names like old yellow enzyme and malic enzyme that give little or no clue as to what reaction was catalyzed were in common use. Most of these names have fallen into disuse, though a few, especially proteolyic enzymes with very low specificity, such as pepsin and papain , are still used, as rational classification on
350-533: The Enzyme Commission was dissolved at that time, though its name lives on in the term EC Number . The current sixth edition, published by the International Union of Biochemistry and Molecular Biology in 1992 as the last version published as a printed book, contains 3196 different enzymes. Supplements 1-4 were published 1993–1999. Subsequent supplements have been published electronically, at the website of
375-670: The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. In August 2018, the IUBMB modified the system by adding the top-level EC 7 category containing translocases. Oxazoline Oxazoline is a five-membered heterocyclic organic compound with the formula C 3 H 5 NO . It is the parent of a family of compounds called oxazolines (emphasis on plural), which contain non-hydrogenic substituents on carbon and/or nitrogen. Oxazolines are
400-584: The basis of specificity has been very difficult. By the 1950s the chaos was becoming intolerable, and after Hoffman-Ostenhof and Dixon and Webb had proposed somewhat similar schemes for classifying enzyme-catalyzed reactions, the International Congress of Biochemistry in Brussels set up the Commission on Enzymes under the chairmanship of Malcolm Dixon in 1955. The first version was published in 1961, and
425-625: The carbohydrate active enzyme classification. Homologs exist in other species as O -GlcNAcase is conserved in higher eukaryotic species. In a pairwise alignment, humans share 55% homology with Drosophila and 43% with C. elegans . Drosophila and C. elegans share 43% homology. Among mammals, the OGA sequence is even more highly conserved. The mouse and the human have 97.8% homology. However, OGA does not share significant homology with other proteins. However, short stretches of about 200 amino acids in OGA have homology with some proteins such as hyaluronidase,
450-443: The functional effects of O -GlcNAc modification is not fully known, it is known that O -GlcNAc modification impacts many cellular activities such as lipid/carbohydrate metabolism and hexosamine biosynthesis. Modified proteins may modulate various downstream signaling pathways by influencing transcription and proteomic activities. OGA catalyzes O -GlcNAc hydrolysis via an oxazoline reaction intermediate. Stable compounds which mimic
475-565: The generic lysosomal hexosaminidases by elongating the C2 substituent in their chemical structure. This takes advantage of a deep pocket in OGA's active site that allow it to bind analogs of GlcNAc. There is potential for regulation of O -GlcNAcase for the treatment of Alzheimer's disease . When the tau protein in the brain is hyperphosphorylated, neurofibrillary tangles form, which are a pathological hallmark for neurodegenerative diseases such as Alzheimer's disease. In order to treat this condition, OGA
500-518: The production of polymers . A fourth isomer exists in which the O and N atoms are adjacent, this is known as isoxazoline . The synthesis of 2-oxazoline rings is well established and in general proceeds via the cyclisation of a 2- amino alcohol (typically obtained by the reduction of an amino acid ) with a suitable functional group. The overall mechanism is usually subject to Baldwin's rules . The usual route to oxazolines entails reaction of acyl chlorides with 2-amino alcohols. Thionyl chloride
525-439: The reaction intermediate can act as selective enzyme inhibitors. Thiazoline derivatives of GlcNAc can be used as a reaction intermediate. An example of this includes Thiamet-G as shown on the right. A second form of inhibition can occur from the mimicry of the transition state . The GlcNAcstatin family of inhibitors exploit this mechanism in order to inhibit OGA activity. For both types of inhibitors, OGA can be selected apart from
SECTION 20
#1733085471046550-433: The reaction. Ligands containing a chiral 2-oxazoline ring are used in asymmetric catalysis due to their facile synthesis, wide range of forms and effectiveness for many types of catalytic transformation. 2-Substituted oxazolines possess a moderately hard N-donor. Chirality is easily incorporated by using 2- amino alcohols prepared by the reduction of amino acids ; which are both optically pure and inexpensive. As
575-470: The same EC number. Furthermore, through convergent evolution , completely different protein folds can catalyze an identical reaction (these are sometimes called non-homologous isofunctional enzymes ) and therefore would be assigned the same EC number. By contrast, UniProt identifiers uniquely specify a protein by its amino acid sequence. Every enzyme code consists of the letters "EC" followed by four numbers separated by periods. Those numbers represent
600-478: The unsaturated analogues of oxazolidines , and they are isomeric with isoxazolines , where the N and O are directly bonded. Two isomers of oxazoline are known, depending on the location of the double bond. Oxazoline itself has no applications however oxazolines have been widely investigated for potential applications. These applications include use as ligands in asymmetric catalysis , as protecting groups for carboxylic acids and increasingly as monomers for
625-508: Was first described by Witte and Seeliger, and further developed by Bolm et al . The reaction requires high temperatures to succeed and is typically performed in refluxing chlorobenzene under anhydrous conditions. A precise reaction mechanism has never been proposed, although it is likely similar to the Pinner reaction ; preceding via an intermediate amidine . Limited research has been done into identifying alternative solvents or catalysts for
#45954