Sandbox Reserved 346: Difference between revisions
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__TOC__ | __TOC__ | ||
=='''Structure'''== | =='''Structure'''== | ||
<Structure load='1b4x' size='300' frame='true' align='left' caption='Figure 1 | <Structure load='1b4x' size='300' frame='true' align='left' caption='Figure 1: Asymetric unit of Aspartate aminotransferase, with highlighted small and large domain and PLP cofactor' scene='Sandbox_Reserved_346/Ast/1'/> | ||
<scene name='Sandbox_Reserved_346/Ast/1'>AST</scene> is a homodimer that contains 16 α-helices and a β-sheet formed from 7 parallel and antiparallel strands<ref name ="AST Structure"/>. Each subunit contains an equivalent active site<ref name ="AST Structure">PMID:2121725</ref>. The subunits connect at two sites: between their large domains and between the N-terminal residues and the large domain on the other subunit<ref name ="AST Structure"/>. This structure of AST varies minutely among organisms ranging from ''E. coli'' to humans<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. As well, the structure of the active site is highly conserved with a sequence homology of 25%<ref name ="AST Structure"/>. | <scene name='Sandbox_Reserved_346/Ast/1'>AST</scene> is a homodimer that contains 16 α-helices and a β-sheet formed from 7 parallel and antiparallel strands<ref name ="AST Structure"/>. Each subunit contains an equivalent active site<ref name ="AST Structure">PMID:2121725</ref>. The subunits connect at two sites: between their large domains and between the N-terminal residues and the large domain on the other subunit<ref name ="AST Structure"/>. This structure of AST varies minutely among organisms ranging from ''E. coli'' to humans<ref name ="AST Structure"/><ref name ="AST ROLES AND STRUCTURE"/>. As well, the structure of the active site is highly conserved with a sequence homology of 25%<ref name ="AST Structure"/>. | ||
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=='''Function'''== | =='''Function'''== | ||
[[Image:Ast-reaction final copy.JPG|right|thumb|upright=3|Figure 2 | [[Image:Ast-reaction final copy.JPG|right|thumb|upright=3|Figure 2: Transamination reaction of L-aspartate and α-ketoglutarate catalyzed by aspartate aminotransferase]] | ||
AST catalyzes the reversible transamination of the α-amino group from L-aspartate to α-ketoglutarate forming oxaloacetate and glutamate<ref name ="AST ROLES AND STRUCTURE"/>. This reactivity is lower in E.coli than in higher eukaryotes, and has broader substrate specificity<ref name ="AST Structure"/>. However, the reaction takes place in the same way<ref name ="AST Structure"/>. Upon introduction of an amino acid substrate, a new Schiff base will form between it and the PLP cofactor<ref name ="AST Structure"/><ref name ="TRANSAMINATION">PMID:5450225</ref>. This causes the amino acid to lose a hydrogen and form a quinoid intermediate, and reprotanation takes place resulting in a ketimine<ref name ="AST Structure"/><ref name ="TRANSAMINATION"/>. Next, the structure is hydrolyzed forming an α-keto acid and pyridoxamine phosphate<ref name ="TRANSAMINATION"/>. 2-methyl aspartate acts as an inhibitor of AST when it forms a Schiif base with the PLP cofactor, rather than aspartate<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. This results in the process stopping at the step prior to the alpha protein elimination<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. | AST catalyzes the reversible transamination of the α-amino group from L-aspartate to α-ketoglutarate forming oxaloacetate and glutamate<ref name ="AST ROLES AND STRUCTURE"/>. This reactivity is lower in E.coli than in higher eukaryotes, and has broader substrate specificity<ref name ="AST Structure"/>. However, the reaction takes place in the same way<ref name ="AST Structure"/>. Upon introduction of an amino acid substrate, a new Schiff base will form between it and the PLP cofactor<ref name ="AST Structure"/><ref name ="TRANSAMINATION">PMID:5450225</ref>. This causes the amino acid to lose a hydrogen and form a quinoid intermediate, and reprotanation takes place resulting in a ketimine<ref name ="AST Structure"/><ref name ="TRANSAMINATION"/>. Next, the structure is hydrolyzed forming an α-keto acid and pyridoxamine phosphate<ref name ="TRANSAMINATION"/>. 2-methyl aspartate acts as an inhibitor of AST when it forms a Schiif base with the PLP cofactor, rather than aspartate<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. This results in the process stopping at the step prior to the alpha protein elimination<ref name ="TRANSAMINATION"/><ref name ="AST Structure"/>. | ||
