3k6m

Publication Abstract from PubMed

The enzyme succinyl-CoA:3-oxoacid coenzyme A transferase (SCOT) participates in the metabolism of ketone bodies in extrahepatic tissues. It catalyses the transfer of coenzyme A (CoA) from succinyl-CoA to acetoacetate with a classical ping-pong mechanism. There is biochemical evidence that the enzyme undergoes conformational changes during the reaction, but no domain movements have been reported in the available crystal structures. Here, a structure of pig heart SCOT refined at 1.5 A resolution is presented, showing that one of the four enzyme subunits in the crystallographic asymmetric unit has a molecule of glycerol bound in the active site; the glycerol molecule is hydrogen bonded to the conserved catalytic glutamate residue and is likely to occupy the cosubstrate-binding site. The binding of glycerol is associated with a substantial relative movement (a 13 degrees rotation) of two previously undefined domains that close around the substrate-binding site. The binding orientation of one of the cosubstrates, acetoacetate, is suggested based on the glycerol binding and the possibility that this dynamic domain movement is of functional importance is discussed.

The high-resolution structure of pig heart succinyl-CoA:3-oxoacid coenzyme A transferase.,Coker SF, Lloyd AJ, Mitchell E, Lewis GR, Coker AR, Shoolingin-Jordan PM Acta Crystallogr D Biol Crystallogr. 2010 Jul;66(Pt 7):797-805. Epub 2010 Jun 19. PMID:20606260^[1]

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