title: The structure of VibH represents nonribosomal peptide synthetase condensation, cyclization and epimerization domains.
abstract: Nonribosomal peptide synthetases (NRPSs) are large, multidomain enzymes that biosynthesize medically important natural products. We report the crystal structure of the free-standing NRPS condensation (C) domain VibH, which catalyzes amide bond formation in the synthesis of vibriobactin, a Vibrio cholerae siderophore. Despite low sequence identity, NRPS condensation enzymes are structurally related to chloramphenicol acetyltransferase (CAT) and dihydrolipoamide acyltransferases. However, although the latter enzymes are homotrimers, VibH is a monomeric pseudodimer. The VibH structure is representative of both NRPS condensation and epimerization domains, as well as the condensation-variant cyclization domains, which are all expected to be monomers. Surprisingly, despite favorable positioning in the active site, a universally conserved histidine important in CAT and in other C domains is not critical for general base catalysis in VibH.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Keating
authors.forename: C Gary
authors.initials: CG
authors.lastname: Marshall
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
authors.forename: Amy E
authors.initials: AE
authors.lastname: Keating
mesh_terms: D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D002396:Catechols / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003500:Cyclization; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D010080:Oxazoles; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents / Q000378:metabolism; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D002396:Catechols; D009097:Multienzyme Complexes; D010080:Oxazoles; D012997:Solvents; C040227:vibriobactin; D000217:Acyltransferases; D010453:Peptide Synthases; D003065:Coenzyme A