6L3M

Crystal Structure of the acyltransferase domain from the third module of the ansamitocin polyketide synthase

Summary for 6L3M

• Entry DOI: 10.2210/pdb6l3m/pdb
• Descriptor: Polyketide synthase, GLYCEROL, 2-methoxypropanedioic acid, ... (5 entities in total)
• Functional Keywords: polyketide, acyltransferase, acp-linked extender unit, carrier specificity, biosynthesis, transferase
• Biological source: Actinosynnema pretiosum subsp. auranticum
• Total number of polymer chains: 4
• Total formula weight: 178136.52

Authors

Zhang, F.,Zheng, J. (deposition date: 2019-10-11, release date: 2019-12-18, Last modification date: 2024-10-16)

Primary citation

Zhang, F.,Ji, H.,Ali, I.,Deng, Z.,Bai, L.,Zheng, J.
Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein-Linked Extender Units in Ansamitocin Biosynthesis.
Chembiochem, 21:1309-1314, 2020

PubMed Abstract: A few acyltransferase (AT) domains of modular polyketide synthases (PKSs) recruit acyl carrier protein (ACP)-linked extender units with unusual C2 substituents to confer functionalities that are not available in coenzyme A (CoA)-linked ones. In this study, an AT specific for methoxymalonyl (MOM)-ACP in the third module of the ansamitocin PKS was structurally and biochemically characterized. The AT uses a conserved tryptophan residue at the entrance of the substrate binding tunnel to discriminate between different carriers. A W275R mutation switches its carrier specificity from the ACP to the CoA molecule. The acyl-AT complex structures clearly show that the MOM-ACP accepted by the AT has the 2S instead of the opposite 2R stereochemistry that is predicted according to the biosynthetic derivation from a d-glycolytic intermediate. Together, these results reveal the structural basis of ATs recognizing ACP-linked extender units in polyketide biosynthesis.

PubMed: 31777147
DOI: 10.1002/cbic.201900628

Experimental method

X-RAY DIFFRACTION (1.77 Å)