title: Interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate: a distinctive B(12)-dependent carbon-skeleton rearrangement.
abstract: The interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate catalyzed by B(12)-dependent glutamate mutase is discussed using results from high-level ab initio molecular orbital calculations. Evidence is presented regarding the possible role of coenzyme-B(12) in substrate activation and product formation via radical generation. Calculated electron paramagnetic resonance parameters support experimental evidence for the involvement of substrate-derived radicals and will hopefully aid the future detection of other important radical intermediates. The height of the rearrangement barrier for a fragmentation-recombination pathway, calculated with a model that includes neutral amino and carboxylic acid substituents in the migrating glycyl group, supports recent experimental evidence for the interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate through such a pathway. Our calculations suggest that the enzyme may facilitate the rearrangement of (S)-glutamate through (partial) proton-transfer processes that control the protonation state of substituents in the migrating group.
authors.affiliation: Contribution from the Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Wetmore
authors.forename: D M
authors.initials: DM
authors.lastname: Smith
authors.forename: B T
authors.initials: BT
authors.lastname: Golding
authors.forename: L
authors.initials: L
authors.lastname: Radom
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D003013:Clostridium / Q000201:enzymology; D003038:Cobamides / Q000378:metabolism; D003839:Deoxyadenosines / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D019751:Intramolecular Transferases / Q000737:chemistry / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011437:Propylamines / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D003038:Cobamides; D003839:Deoxyadenosines; D011437:Propylamines; C018934:3-methylaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C033714:5'-deoxyadenosine; D006859:Hydrogen; D019751:Intramolecular Transferases; C021570:methylaspartate mutase; D008765:Methylmalonyl-CoA Mutase; C047997:2-methyleneglutarate mutase; D005998:Glycine