Novel domain arrangement in the crystal structure of a truncated acetyl-CoA synthase from Moorella thermoacetica.
Ni-dependent acetyl-CoA synthase (ACS) and CO dehydrogenase (CODH) constitute the central enzyme complex of the Wood-Ljungdahl pathway of acetyl-CoA formation. The crystal structure of a recombinant bacterial ACS lacking the N-terminal domain that interacts with CODH shows a large reorganization of the remaining two globular domains, producing a narrow cleft of suitable size, shape, and nature to bind CoA. Sequence comparisons with homologous archaeal enzymes that naturally lack the N-terminal domain show that many amino acids lining this cleft are conserved. Besides the typical [4Fe-4S] center, the A-cluster contains only one proximal metal ion that, according to anomalous scattering data, is most likely Cu or Zn. Incorporation of a functional Ni(2)Fe(4)S(4) A-cluster would require only minor structural rearrangements. Using available structures, a plausible model of the interaction between CODH and the smaller ACS in archaeal multienzyme complexes is presented, along with a discussion of evolutionary relationships of the archaeal and bacterial enzymes.
Volbeda
Anne
A
Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, Université Joseph Fourier, 41 Rue Jules Horowitz, F-38027 Grenoble, France. anne.volbeda@ibs.fr
Darnault
Claudine
C
Tan
Xiangshi
X
Lindahl
Paul A
PA
Fontecilla-Camps
Juan C
JC
D000106:Acetate-CoA Ligase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D000106:Acetate-CoA Ligase