title: The crystal structure of the Escherichia coli YfdW gene product reveals a new fold of two interlaced rings identifying a wide family of CoA transferases.
abstract: Because of its toxicity, oxalate accumulation from amino acid catabolism leads to acute disorders in mammals. Gut microflora are therefore pivotal in maintaining a safe intestinal oxalate balance through oxalate degradation. Oxalate catabolism was first identified in Oxalobacter formigenes, a specialized, strictly anaerobic bacterium. Oxalate degradation was found to be performed successively by two enzymes, a formyl-CoA transferase (frc) and an oxalate decarboxylase (oxc). These two genes are present in several bacterial genomes including that of Escherichia coli. The frc ortholog in E. coli is yfdW, with which it shares 61% sequence identity. We have expressed the YfdW open reading frame product and solved its crystal structure in the apo-form and in complex with acetyl-CoA and with a mixture of acetyl-CoA and oxalate. YfdW exhibits a novel and spectacular fold in which two monomers assemble as interlaced rings, defining the CoA binding site at their interface. From the structure of the complex with acetyl-CoA and oxalate, we propose a putative formyl/oxalate transfer mechanism involving the conserved catalytic residue Asp169. The similarity of yfdW with bacterial orthologs (approximately 60% identity) and paralogs (approximately 20-30% identity) suggests that this new fold and parts of the CoA transfer mechanism are likely to be the hallmarks of a wide family of CoA transferases.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, UMR 6098, CNRS and Universités Aix-Marseille I and II, 31 chemin J. Aiguier, F-13402 Marseille, Cedex 20, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gruez
authors.forename: Véronique
authors.initials: V
authors.lastname: Roig-Zamboni
authors.forename: Christel
authors.initials: C
authors.lastname: Valencia
authors.forename: Valérie
authors.initials: V
authors.lastname: Campanacci
authors.forename: Christian
authors.initials: C
authors.lastname: Cambillau
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D003001:Cloning, Molecular; D015256:Coenzyme A-Transferases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D016680:Genome, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010070:Oxalates / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D029968:Escherichia coli Proteins; D010070:Oxalates; D000105:Acetyl Coenzyme A; D015256:Coenzyme A-Transferases; C477746:YfdW protein, E coli