Formyl-CoA transferase encloses the CoA binding site at the interface of an interlocked dimer.
Formyl-CoA transferase catalyses transfer of CoA from formate to oxalate in the first step of oxalate degradation by Oxalobacter formigenes, a bacterium present in the intestinal flora which is implicated in oxalate catabolism in mammals. Formyl-CoA transferase is a member of a family of CoA-transferases for which no structural information is available. We now report the three-dimensional structure of O.formigenes formyl-CoA transferase, which reveals a novel fold and a very striking assembly of the homodimer. The subunit is composed of a large and a small domain where residues from both the N- and C-termini of the subunit are part of the large domain. The linkers between the domains give the subunit a circular shape with a hole in the middle. The enzyme monomers are tightly interacting and are interlocked. This fold requires drastic rearrangement of approximately 75 residues at the C-terminus for formation of the dimer. The structure of a complex of formyl-CoA transferase with CoA is also reported and sets the scene for a mechanistic understanding of enzymes of this family of CoA-transferases.
Ricagno
Stefano
S
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
Jonsson
Stefan
S
Richards
Nigel
N
Lindqvist
Ylva
Y
D000595:Amino Acid Sequence; D001665:Binding Sites; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D011994:Recombinant Proteins; D015256:Coenzyme A-Transferases; C064813:formyl-coenzyme A transferase; D003065:Coenzyme A