Mutagenesis Supports AlphaFold Prediction of How Modular Polyketide Synthase Acyl Carrier Proteins Dock With Downstream Ketosynthases.

ABSTRACT: The docking of an acyl carrier protein (ACP) domain with a downstream ketosynthase (KS) domain in each module of a polyketide synthase (PKS) helps ensure accurate biosynthesis. If the polyketide chain bound to the ACP has been properly modified by upstream processing enzymes and is compatible with gatekeeping residues in the KS tunnel, a transacylation reaction can transfer it from the 18.1-Å phosphopantetheinyl arm of the ACP to the reactive cysteine of the KS. AlphaFold-Multimer predicts a general interface for these transacylation checkpoints. Half of the solutions obtained for 50 ACP/KS pairs show the KS motif TxLGDP forming the first turn of an α-helix, as in reported structures, while half show it forming a type I β-turn not previously observed. Solutions with the latter conformation

SUBMITTER: Hirsch M 

PROVIDER: S-EPMC11543512 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature