8IN9

The structure of the GfsA KSQ-AT didomain in complex with the GfsA ACP domain

Summary for 8IN9

• Entry DOI: 10.2210/pdb8in9/pdb
• Descriptor: Polyketide synthase, N-[2-(acetylamino)ethyl]-N~3~-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alaninamide (3 entities in total)
• Functional Keywords: decarboxylase, complex, polyketide synthase, lyase
• Biological source: Streptomyces graminofaciens; More
• Total number of polymer chains: 2
• Total formula weight: 105523.65

Authors

Chisuga, T.,Murakami, S.,Miyanaga, A.,Kudo, F.,Eguchi, T. (deposition date: 2023-03-09, release date: 2023-05-31, Last modification date: 2024-11-20)

Primary citation

Chisuga, T.,Murakami, S.,Miyanaga, A.,Kudo, F.,Eguchi, T.
Structure-Based Analysis of Transient Interactions between Ketosynthase-like Decarboxylase and Acyl Carrier Protein in a Loading Module of Modular Polyketide Synthase.
Acs Chem.Biol., 18:1398-1404, 2023

PubMed Abstract: Ketosynthase-like decarboxylase (KS) domains are widely distributed in the loading modules of modular type I polyketide synthases (PKSs) and catalyze the decarboxylation of the (alkyl-)malonyl unit bound to the acyl carrier protein (ACP) in the loading module for the construction of the PKS starter unit. Previously, we performed a structural and functional analysis of the GfsA KS domain involved in the biosynthesis of macrolide antibiotic FD-891. We furthermore revealed the recognition mechanism for the malonic acid thioester moiety of the malonyl-GfsA loading module ACP (ACP) as a substrate. However, the exact recognition mechanism for the GfsA ACP moiety remains unclear. Here, we present a structural basis for the interactions between the GfsA KS domain and GfsA ACP. We determined the crystal structure of the GfsA KS-acyltransferase (AT) didomain in complex with ACP (ACP=KSAT complex) by using a pantetheine crosslinking probe. We identified the key amino acid residues involved in the KS domain-ACP interactions and confirmed the importance of these residues by mutational analysis. The binding mode of ACP to the GfsA KS domain is similar to that of ACP to the ketosynthase domain in modular type I PKSs. Furthermore, comparing the ACP=KSAT complex structure with other full-length PKS module structures provides important insights into the overall architectures and conformational dynamics of the type I PKS modules.

PubMed: 37216195
DOI: 10.1021/acschembio.3c00151

Experimental method

X-RAY DIFFRACTION (3.4 Å)