The structure of VibH represents nonribosomal peptide synthetase condensation, cyclization and epimerization domains.
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.
Keating
Thomas A
TA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Marshall
C Gary
CG
Walsh
Christopher T
CT
Keating
Amy E
AE
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*
D002396:Catechols; D009097:Multienzyme Complexes; D010080:Oxazoles; D012997:Solvents; C040227:vibriobactin; D000217:Acyltransferases; D010453:Peptide Synthases; D003065:Coenzyme A