Gating mechanism of elongating ß-ketoacyl-ACP synthases.
Nat Commun
; 11(1): 1727, 2020 04 07.
Article
em En
| MEDLINE
| ID: mdl-32265440
ABSTRACT
Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, ß-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs.
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Base de dados:
MEDLINE
Assunto principal:
3-Oxoacil-(Proteína de Transporte de Acila) Sintase
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Acetiltransferases
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Proteínas de Escherichia coli
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Escherichia coli
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Ácido Graxo Sintase Tipo II
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article