M-CSA Mechanism and Catalytic Site Atlas

Formyl-CoA transferase

Formyl-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 carbon dioxide - other carbohydrates cannot be used to replace oxalate as a growth substrate, implying that the organism lacks a functional glycolytic pathway.

Reference Protein and Structure

Sequence: O06644 (2.8.3.16) (Sequence Homologues) (PDB Homologues)
Biological species: Oxalobacter formigenes (Bacteria)
PDB: 1t4c - Formyl-CoA Transferase in complex with Oxalyl-CoA (2.61 Å)
Catalytic CATH Domains: 3.30.1540.10 3.40.50.10540 (see all for 1t4c)

Click To Show Structure

Enzyme Reaction (EC:2.8.3.16)

oxalate(2-)

CHEBI:30623

formyl-CoA(4-)

CHEBI:57376

→

oxalyl-CoA(5-)

CHEBI:57388

formate

CHEBI:15740

Enzyme reaction links: IntEnz ENZYME ExplorEnz

Alternative enzyme names: Formyl-CoA oxalate CoA-transferase, Formyl-coenzyme A transferase,

Summary
Step 1
Step 2
Step 3
Step 4
Step 5
Step 6
Step 7
Step 8
Products
All Steps

Introduction

This mechanism proposal differs from the other in the fact that when CoAS is originally cleaved in the first elimination it then re-attacks the carbonyl carbon so that formate will be eliminated in the next step. Then oxalate will nucleophilically attack Asp169 and CoAS will be cleaved again so that it can re-attack at the carbonyl carbon of oxalate so that Asp169 can be cleaved from the intermediate and release the final product of oxalyl-CoA. This mechanism has been shown to be relevant for Class III CoA-transferases which Formyl-CoA transferase is an example of whereas the previous proposal is an example of class I CoA-transferases (PMID: 18162462)

Catalytic Residues Roles

UniProt	PDB* (1t4c)
Glu140 (main-N)	Glu140(139)A (main-N)	Glu 140 stabilises O1 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide	hydrogen bond donor
Gly260 (main-C)	Gly260(259)B (main-C)	Gly 260' stabilises O2 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone carbonyl.	hydrogen bond acceptor
Gly261 (main-N)	Gly261(260)B (main-N)	Gly 261' stabilises O2 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide	hydrogen bond donor
Gln17	Gln17(16)A	Gln 17 stabilises O3 of the oxalyl part of the oxalyl aspartic anhydride through hydrogen bonding to the backbone amide.	hydrogen bond donor, electrostatic stabiliser
Asp169	Asp169(168)A	Asp 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 and CoAS.	covalently attached, nucleofuge, nucleophile, electrofuge, electrophile

*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

bimolecular nucleophilic addition, overall reactant used, enzyme-substrate complex formation, intermediate formation, unimolecular elimination by the conjugate base, enzyme-substrate complex cleavage, intermediate collapse, overall product formed, intermediate terminated, native state of enzyme regenerated

References

Berthold CL et al. (2008), J Biol Chem, 283, 6519-6529. Reinvestigation of the catalytic mechanism of formyl-CoA transferase, a class III CoA-transferase. DOI:10.1074/jbc.M709353200. PMID:18162462.

Step 1. Asp169 attacks the carbonyl carbon of formyl-CoA in a nucleophilic addition.

Formyl-CoA transferase

Reference Protein and Structure

Enzyme Reaction (EC:2.8.3.16)

Enzyme Mechanism

Introduction

Catalytic Residues Roles

Chemical Components

References

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Introduction

Catalytic Residues Roles

Chemical Components

References

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Catalytic Residues Roles

Chemical Components

Contributors