Mechanism of controlled radical initiation in radical SAM GTP 3',8-cyclase.

ABSTRACT: Metalloenzymes couple substrate binding and formation of oxidative intermediates to minimize unwanted side reactions. However, the molecular details of such coupling frequently remain ambiguous. Radical S-adenosyl-L-methionine (SAM) enzymes constitute one of the largest groups of metalloenzymes and catalyze various radical-mediated reactions. While radical SAM enzymes significantly accelerate the conserved radical initiation reaction, the reductive cleavage of SAM into 5'-deoxyadenosyl radical (5'-dA•), the molecular mechanism of this rate acceleration is largely unexplored. Here, using MoaA, aradical SAM enzyme in the molybdenum cofactor (Moco) biosynthesis, as a model, we reveal the mechanism of substrate-triggered radical initiation. We first elucidated the intact active site str

SUBMITTER: Pang H 

PROVIDER: S-EPMC12625886 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature