The synthetase domains of cobalamin biosynthesis amidotransferases cobB and cobQ belong to a new family of ATP-dependent amidoligases, related to dethiobiotin synthetase.
Phosphotransacetylases of Escherichia coli and several other bacteria contain an additional 350-aa N-terminal fragment that is not required for phosphotransacetylase activity. Sequence analysis of this fragment revealed that it is closely related to a family of ATP-dependent enzymes that also includes dethiobiotin synthetase and the synthetase domains of two amidotransferases involved in cobalamin biosynthesis, cobyrinic acid a,c-diamide synthase (CobB) and cobyric acid synthase (CobQ). Further database searches showed that this enzyme family is also related to the MinD family of ATPases involved in regulation of cell division in bacteria and archaea. Analysis of sequence conservation in the members of this enzyme family using the structure of dethiobiotin synthetase active site as a guide allowed us to suggest a model for the interaction of CobB and CobQ with their respective substrates. CobB and CobQ were also found to contain unusual Triad family (class I) glutamine amidotransferase domains with conserved Cys and His residues, but lacking the Glu residue of the catalytic triad. These results should help in understanding the enzymology of cobalamin biosynthesis and in resolving the role of phosphotransacetylase in regulation of the carbon flow to and from acetate.
Galperin
M Y
MY
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. galperin@ncbi.nlm.nih.gov
Grishin
N V
NV
D000251:Adenosine Triphosphatases / Q000737:chemistry; D000595:Amino Acid Sequence; D001105:Archaea / Q000737:chemistry; D001419:Bacteria / Q000737:chemistry; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry*; D017124:Conserved Sequence; D029968:Escherichia coli Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010709:Phosphate Acetyltransferase / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D000637:Transaminases / Q000737:chemistry*; D014805:Vitamin B 12 / Q000096:biosynthesis*
D029968:Escherichia coli Proteins; D010709:Phosphate Acetyltransferase; D000637:Transaminases; C071151:cobyric acid synthase; C065829:cobyrinic acid a,c-diamide synthase; D000251:Adenosine Triphosphatases; C072069:MinD protein, E coli; D019731:Carbon-Nitrogen Ligases; C020024:dethiobiotin synthetase; D014805:Vitamin B 12