title: Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases.
abstract: The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.
authors.affiliation: Cambridge Centre for Molecular Recognition, Department of Biochemistry, University of Cambridge, UK.
authors.forename: S F
authors.initials: SF
authors.lastname: Haydock
authors.forename: J F
authors.initials: JF
authors.lastname: Aparicio
authors.forename: I
authors.initials: I
authors.lastname: Molnár
authors.forename: T
authors.initials: T
authors.lastname: Schwecke
authors.forename: L E
authors.initials: LE
authors.lastname: Khaw
authors.forename: A
authors.initials: A
authors.lastname: König
authors.forename: A F
authors.initials: AF
authors.lastname: Marsden
authors.forename: I S
authors.initials: IS
authors.lastname: Galloway
authors.forename: J
authors.initials: J
authors.lastname: Staunton
authors.forename: P F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism; D051080:Acyl-Carrier Protein S-Malonyltransferase; D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; D009097:Multienzyme Complexes; D008316:Malonyl Coenzyme A; D000217:Acyltransferases; D051080:Acyl-Carrier Protein S-Malonyltransferase