Structure-Based Demystification of Radical Catalysis by a Coenzyme B₁₂ Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.

ABSTRACT: Catalysis 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 10¹²-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 radi

SUBMITTER: Gruber K 

PROVIDER: S-EPMC10947579 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature