Details

Autor(en) / Beteiligte

• Martins, Berta M.
• Dobbek, Holger
• Çinkaya, Irfan
• Buckel, Wolfgang
• Messerschmidt, Albrecht
• Beinert, Helmut

Titel

Crystal Structure of 4-Hydroxybutyryl-CoA Dehydratase: Radical Catalysis Involving a [4Fe-4S] Cluster and Flavin

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-11, Vol.101 (44), p.15645-15649

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 [4 Fe-4 S]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 [4 Fe-4 S]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.