title: A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity.
abstract: The recently developed PSI-BLAST method for sequence database search and methods for motif analysis were used to define and expand a superfamily of enzymes with an unusual nucleotide-binding fold, referred to as palmate, or ATP-grasp fold. In addition to D-alanine-D-alanine ligase, glutathione synthetase, biotin carboxylase, and carbamoyl phosphate synthetase, enzymes with known three-dimensional structures, the ATP-grasp domain is predicted in the ribosomal protein S6 modification enzyme (RimK), urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis. All these enzymes possess ATP-dependent carboxylate-amine ligase activity, and their catalytic mechanisms are likely to include acylphosphate intermediates. The ATP-grasp superfamily also includes succinate-CoA ligase (both ADP-forming and GDP-forming variants), malate-CoA ligase, and ATP-citrate lyase, enzymes with a carboxylate-thiol ligase activity, and several uncharacterized proteins. These findings significantly extend the variety of the substrates of ATP-grasp enzymes and the range of biochemical pathways in which they are involved, and demonstrate the complementarity between structural comparison and powerful methods for sequence analysis.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. galperin@ncbi.nlm.nih.gov
authors.forename: M Y
authors.initials: MY
authors.lastname: Galperin
authors.forename: E V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001665:Binding Sites; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017421:Sequence Analysis; D013329:Structure-Activity Relationship
chemical_list: D000255:Adenosine Triphosphate; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase