2fpp
Crystal structure of pig GTP-specific succinyl-CoA synthetase from polyethylene glycol with chloride ions
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OverviewOverview
Two isoforms of succinyl-CoA synthetase exist in mammals, one specific for ATP and the other for GTP. The GTP-specific form of pig succinyl-CoA synthetase has been crystallized in the presence of GTP and the structure determined to 2.1 A resolution. GTP is bound in the ATP-grasp domain, where interactions of the guanine base with a glutamine residue (Gln-20beta) and with backbone atoms provide the specificity. The gamma-phosphate interacts with the side chain of an arginine residue (Arg-54beta) and with backbone amide nitrogen atoms, leading to tight interactions between the gamma-phosphate and the protein. This contrasts with the structures of ATP bound to other members of the family of ATP-grasp proteins where the gamma-phosphate is exposed, free to react with the other substrate. To test if GDP would interact with GTP-specific succinyl-CoA synthetase in the same way that ADP interacts with other members of the family of ATP-grasp proteins, the structure of GDP bound to GTP-specific succinyl-CoA synthetase was also determined. A comparison of the conformations of GTP and GDP shows that the bases adopt the same position but that changes in conformation of the ribose moieties and the alpha- and beta-phosphates allow the gamma-phosphate to interact with the arginine residue and amide nitrogen atoms in GTP, while the beta-phosphate interacts with these residues in GDP. The complex of GTP with succinyl-CoA synthetase shows that the enzyme is able to protect GTP from hydrolysis when the active-site histidine residue is not in position to be phosphorylated.
About this StructureAbout this Structure
2FPP is a Protein complex structure of sequences from Sus scrofa with and as ligands. Active as Succinate--CoA ligase (GDP-forming), with EC number 6.2.1.4 Full crystallographic information is available from OCA.
ReferenceReference
Interactions of GTP with the ATP-grasp domain of GTP-specific succinyl-CoA synthetase., Fraser ME, Hayakawa K, Hume MS, Ryan DG, Brownie ER, J Biol Chem. 2006 Apr 21;281(16):11058-65. Epub 2006 Feb 15. PMID:16481318
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