6h9f
From Proteopedia
Structure of glutamate mutase reconstituted with bishomo-coenzyme B12
Structural highlights
FunctionGLME_CLOCO Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate).[1] [2] Publication Abstract from PubMedCatalysis by radical enzymes dependent on coenzyme B12 (AdoCbl) relies on the reactive primary 5'-deoxy-5'adenosyl radical, which originates from reversible Co-C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 10(12) -fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic. As revealed here, a displaced firm adenosine binding cavity in substrate-loaded glutamate mutase (GM) causes a structural misfit for intact AdoCbl that is relieved by the homolytic Co-C bond cleavage. Strategically interacting adjacent adenosine- and substrate-binding protein cavities provide a tight caged radical reaction space, controlling the entire radical path. The GM active site is perfectly structured for promoting radical catalysis, including "negative catalysis", a paradigm for AdoCbl-dependent mutases. Structure-Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.,Gruber K, Csitkovits V, Lyskowski A, Kratky C, Krautler B Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi:, 10.1002/anie.202208295. Epub 2022 Jul 21. PMID:35793207[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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