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Catalytic Site Atlas

CSA LITERATURE entry for 1t4c

E.C. nameformyl-CoA transferase
SpeciesOxalobacter formigenes (Bacteria)
E.C. Number (IntEnz) 2.8.3.16
CSA Homologues of 1t4c
CSA Entries With UniProtID O06644
CSA Entries With EC Number 2.8.3.16
PDBe Entry 1t4c
PDBSum Entry 1t4c
MACiE Entry M0155

Literature Report

IntroductionFormyl-CoA Transferase, sourced from Oxalobacter formigenes colonises the human gastrointestinal tract. It breaks down oxalate to generate ATP. Formyl-CoA Transferase is a critical enzyme in oxalate-dependent ATP synthesis. It catalyses the transfer of CoA from formyl-CoA to oxalate, producing oxalyl-CoA and formate. It is of interest due to a correlation between absence of O. formigenes in humans and kidney stone formation due to elevated levels of oxalate in the blood. Secondly ATP production appears to depend solely on the anaerobic conversion of oxalate to formate and CO2 - other carbohydrates cannot be used to replace oxalate as a growth substrate, implying that the organism lacks a functional glycolytic pathway.
Mechansim1. Asp 169 performs nucleophilic attack upon formyl-CoA, attacking the carbonyl group of the thioester. A tetrahedral oxyanion transition state is formed. It is unclear how the transition state is stabilised. The transition state collapses and the thiol-CoA group leaves. 2. Oxalate performs nucleophilic attack upon the electrophilic carbonyl group of Asp 169, within the anhydride intermediate. A tetrahedral oxyanion transition state is formed. The transition state collapses and the formate leaves. A second anhydride intermediate is formed. This is stabilised by hydrogen bonding of the oxalyl part of the oxalyl aspartic anhydride to stabilising residues. O1 is stabilised by hydrogen bonding to the backbone amide of Glu 140, O2 to the amide of Gly 261' and backbone carbonyl of Gly 260' and O3 to the backbone amide of Gln 17. 3. Thiol-CoA performs nucleophilic attack upon the carbonyl group of oxalate, within the anhydride intermediate. A tetrahedral oxyanion transition state is formed. The transition state collapses and the Asp 169 residue leaves.
Reaction

Catalytic Sites for 1t4c

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnA1717macie:mainChainAmideGln 17 stabilises O3 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide.
GluA140140macie:mainChainAmideGlu 140 stabilises O1 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide.
AspA169169macie:sideChainAsp 169 performs nucleophilic attack upon formyl-CoA, attacking the carbonyl group of the thioester. The electrophilic carbonyl group of Asp 169 is nucleophilically attacked by oxalate.
GlyB260260macie:mainChainAmideGly 260' stabilises O2 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone carbonyl.
GlyB261261macie:mainChainAmideGly 261' stabilises O2 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA260260macie:sideChainError
GlyA261261macie:sideChainError
GlnB1717macie:sideChainError
GluB140140macie:sideChainError

Literature References

Notes:It is still not known how the enzyme stabilises the three tetrahedral transition states. There is evidence for the proposal that attack of the Asp 169 carboxylate on formyl-CoA proceeds via a concerted mechanism in which an oxyanion transition state is not formed, but further experimentation is needed.
Jonsson S
Kinetic and mechanistic characterization of the formyl-CoA transferase from Oxalobacter formigenes.
J Biol Chem 2004 279 36003-36012
PubMed: 15213226
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