Evolution of function in the crotonase superfamily: the stereochemical course of the reaction catalyzed by 2-ketocyclohexanecarboxyl-CoA hydrolase.
Members of the mechanistically diverse enoyl-CoA hydratase (crotonase) superfamily catalyze reactions that involve stabilization of an enolate anion derived from an acyl thioester of coenzyme A. 2-Ketocyclohexanecarboxyl-CoA hydrolase (BadI), found in a pathway for anaerobic degradation of benzoate by Rhodopseudomonas palustris, is a member of the crotonase superfamily that catalyzes a reverse Dieckmann reaction in which the substrate is hydrolyzed to pimelyl-CoA. The substrate is the configurationally labile 2S-ketocyclohexanecarboxyl-CoA, and in 2H2O solvent hydrogen is incorporated into the 2-proS position of the pimelyl-CoA product. Therefore, the stereochemical course of the BadI-catalyzed reaction is inversion. This information is important for understanding the roles of active-site functional groups in the active site of BadI as well as in the active sites of the homologous 1,4-dihydroxynaphthoyl-CoA synthases that catalyze a forward Dieckmann reaction.
Eberhard
Ellen D
ED
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA.
Gerlt
John A
JA
D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003903:Deuterium / Q000737:chemistry; D004746:Enoyl-CoA Hydratase / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D013869:Thiolester Hydrolases / Q000737:chemistry* / Q000378:metabolism*
D000214:Acyl Coenzyme A; C112169:pimelyl-coenzyme A; D003903:Deuterium; C106551:2-ketocyclohexanecarboxyl-coenzyme A hydrolase; D013869:Thiolester Hydrolases; D004746:Enoyl-CoA Hydratase