3oxo

Publication Abstract from PubMed

Catalysis by succinyl-CoA:3-oxoacid CoA transferase proceeds through a thioester intermediate in which CoA is covalently linked to the enzyme. To determine the conformation of the thioester intermediate, crystals of the pig enzyme were grown in the presence of the substrate acetoacetyl-CoA. X-ray diffraction data show the enzyme in both the free form and covalently bound to CoA via Glu305. In the complex, the protein adopts a conformation in which residues 267-275, 280-287, 357-373 and 398-477 have shifted towards Glu305, closing the enzyme around the thioester. Enzymes provide catalysis by stabilizing the transition state relative to complexes with substrates or products. In this case, the conformational change allows the enzyme to interact with parts of CoA distant from the reactive thiol while the thiol is covalently linked to the enzyme. The enzyme forms stabilizing interactions with both the nucleotide and pantoic acid portions of CoA, while the interactions with the amide groups of the pantetheine portion are poor. The results shed light on how the enzyme uses the binding energy for groups remote from the active center of CoA to destabilize atoms closer to the active centre, leading to acceleration of the reaction by the enzyme.

Catalytic Role of the Conformational Change in Succinyl-CoA:3-Oxoacid CoA Transferase on Binding CoA.,Fraser ME, Hayakawa K, Brown WD Biochemistry. 2010 Oct 26. PMID:20977214^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.