Crystal structure of 4-hydroxybutyryl-CoA dehydratase: Radical catalysis involving a [4Fe–4S] cluster and flavin

AUTOR(ES)

Martins, Berta M.

FONTE

National Academy of Sciences

RESUMO

Dehydratases catalyze the breakage of a carbon—oxygen bond leading to unsaturated products via the elimination of water. The 1.6-Å resolution crystal structure of 4-hydroxybutyryl-CoA dehydratase from the γ-aminobutyrate-fermenting Clostridium aminobutyricum represents a new class of dehydratases with an unprecedented active site architecture. A [4Fe–4S]2+ cluster, coordinated by three cysteine and one histidine residues, is located 7 Å from the Re-side of a flavin adenine dinucleotide (FAD) moiety. The structure provides insight into the function of these ubiquitous prosthetic groups in the chemically nonfacile, radical-mediated dehydration of 4-hydroxybutyryl-CoA. The substrate can be bound between the [4Fe–4S]2+ cluster and the FAD with both cofactors contributing to its radical activation and catalytic conversion. Our results raise interesting questions regarding the mechanism of acyl-CoA dehydrogenases, which are involved in fatty acid oxidation, and address the divergent evolution of the ancestral common gene.

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