3OXO

Succinyl-CoA:3-ketoacid CoA transferase from pig heart covalently bound to CoA

Summary for 3OXO

• Entry DOI: 10.2210/pdb3oxo/pdb
• Related: 1m3e 1ooy 1ooz 1ope 2nrb 2nrc
• Descriptor: Succinyl-CoA:3-ketoacid-coenzyme A transferase 1, mitochondrial, CHLORIDE ION, COENZYME A, ... (4 entities in total)
• Functional Keywords: alpha/beta protein, transferase
• Biological source: Sus scrofa (swine,wild boar)
• Cellular location: Mitochondrion: Q29551
• Total number of polymer chains: 8
• Total formula weight: 429896.93

Authors

Fraser, M.E. (deposition date: 2010-09-21, release date: 2010-11-10, Last modification date: 2024-11-06)

Primary citation

Fraser, M.E.,Hayakawa, K.,Brown, W.D.
Catalytic role of the conformational change in succinyl-CoA:3-oxoacid CoA transferase on binding CoA.
Biochemistry, 49:10319-10328, 2010

PubMed Abstract: 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 toward 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 center, leading to acceleration of the reaction by the enzyme.

PubMed: 20977214
DOI: 10.1021/bi100659s

Experimental method

X-RAY DIFFRACTION (2.3 Å)