Mutagenesis Supports AlphaFold Prediction of How Modular Polyketide Synthase Acyl Carrier Proteins Dock With Downstream Ketosynthases.
AlphaFold
acyl carrier protein
domain–domain interface
ketosynthase
modular polyketide synthase
Journal
Proteins
ISSN: 1097-0134
Titre abrégé: Proteins
Pays: United States
ID NLM: 8700181
Informations de publication
Date de publication:
30 Jul 2024
30 Jul 2024
Historique:
revised:
07
06
2024
received:
14
02
2024
accepted:
05
07
2024
medline:
30
7
2024
pubmed:
30
7
2024
entrez:
30
7
2024
Statut:
aheadofprint
Résumé
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 may represent how these domains are relatively positioned during the transacylation reaction, as the entrance to the KS active site is relatively open and the phosphopantetheinylated ACP serine and the reactive KS cysteine are relatively closer-17.2 versus 20.9 Å, on average. To probe the predicted interface, 20 mutations were made to KS surface residues within the model triketide lactone synthase P1-P6-P7. The activities of these mutants are consistent with the proposed interface.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : GM106112
Pays : United States
Organisme : Welch Foundation
ID : F-1712
Informations de copyright
© 2024 Wiley Periodicals LLC.
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