1M3E

Succinyl-COA:3-ketoacid COA transferase from pig heart (selenomethionine)

Summary for 1M3E

• Entry DOI: 10.2210/pdb1m3e/pdb
• Descriptor: SUCCINYL-COA:3-KETOACID-COENZYME A TRANSFERASE (2 entities in total)
• Functional Keywords: alpha/beta protein, transferase
• Biological source: Sus scrofa (pig)
• Cellular location: Mitochondrion: Q29551
• Total number of polymer chains: 4
• Total formula weight: 211614.34

Authors

Bateman, K.S.,Brownie, E.R.,Wolodko, W.T.,Fraser, M.E. (deposition date: 2002-06-27, release date: 2003-01-07, Last modification date: 2017-10-11)

Primary citation

Bateman, K.S.,Brownie, E.R.,Wolodko, W.T.,Fraser, M.E.
Structure of the Mammalian CoA Transferase from Pig Heart
Biochemistry, 41:14455-14462, 2002

PubMed Abstract: Ketoacidosis affects patients who are deficient in the enzyme activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT), since SCOT catalyses the activation of acetoacetate in the metabolism of ketone bodies. Thus far, structure/function analysis of the mammalian enzyme has been predicted based on the three-dimensional structure of a CoA transferase determined from an anaerobic bacterium that utilizes its enzyme for glutamate fermentation. To better interpret clinical data, we have determined the structure of a mammalian CoA transferase from pig heart by X-ray crystallography to 2.5 A resolution. Instrumental to the structure determination were selenomethionine substitution and the use of argon during purification and crystallization. Although pig heart SCOT adopts an alpha/beta protein fold, resembling the overall fold of the bacterial CoA transferase, several loops near the active site of pig heart SCOT follow different paths than the corresponding loops in the bacterial enzyme, accounting for differences in substrate specificities. Two missense mutations found associated with SCOT of ketoacidosis patients were mapped to a location in the structure that might disrupt the stabilization of the amino-terminal strand and thereby interfere with the proper folding of the protein into a functional enzyme.

PubMed: 12463743
DOI: 10.1021/bi020568f

Experimental method

X-RAY DIFFRACTION (2.5 Å)