4MZ0

Structure of a ketosynthase-acyltransferase di-domain from module CurL of the curacin A polyketide synthase

Summary for 4MZ0

• Entry DOI: 10.2210/pdb4mz0/pdb
• Related: 4MYY 4MYZ
• Descriptor: CurL, CALCIUM ION (3 entities in total)
• Functional Keywords: ketosynthase, thiolase fold, acyltransferase, alpha/beta hydrolase fold, extension of polyketide intermediate, transferase
• Biological source: Moorea producens 3L
• Total number of polymer chains: 2
• Total formula weight: 204150.22

Authors

Whicher, J.R.,Smaga, S.S.,Smith, J.L. (deposition date: 2013-09-28, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

Whicher, J.R.,Smaga, S.S.,Hansen, D.A.,Brown, W.C.,Gerwick, W.H.,Sherman, D.H.,Smith, J.L.
Cyanobacterial polyketide synthase docking domains: a tool for engineering natural product biosynthesis.
Chem.Biol., 20:1340-1351, 2013

PubMed Abstract: Modular type I polyketide synthases (PKSs) are versatile biosynthetic systems that initiate, successively elongate, and modify acyl chains. Intermediate transfer between modules is mediated via docking domains, which are attractive targets for PKS pathway engineering to produce natural product analogs. We identified a class 2 docking domain in cyanobacterial PKSs and determined crystal structures for two docking domain pairs, revealing a distinct class 2 docking strategy for promoting intermediate transfer. The selectivity of class 2 docking interactions, demonstrated in binding and biochemical assays, could be altered by mutagenesis. We determined the ideal fusion location for exchanging class 1 and class 2 docking domains and demonstrated effective polyketide chain transfer in heterologous modules. Thus, class 2 docking domains are tools for rational bioengineering of a broad range of PKSs containing either class 1 or 2 docking domains.

PubMed: 24183970
DOI: 10.1016/j.chembiol.2013.09.015

Experimental method

X-RAY DIFFRACTION (2.8 Å)