6ECT

StiE O-MT residues 961-1257

Summary for 6ECT

• Entry DOI: 10.2210/pdb6ect/pdb
• Descriptor: StiE protein, S-ADENOSYLMETHIONINE (3 entities in total)
• Functional Keywords: methyltransferase, transferase
• Biological source: Stigmatella aurantiaca
• Total number of polymer chains: 1
• Total formula weight: 36984.38

Authors

Skiba, M.A.,Bivins, M.M.,Smith, J.L. (deposition date: 2018-08-08, release date: 2018-12-12, Last modification date: 2024-03-13)

Primary citation

Skiba, M.A.,Bivins, M.M.,Schultz, J.R.,Bernard, S.M.,Fiers, W.D.,Dan, Q.,Kulkarni, S.,Wipf, P.,Gerwick, W.H.,Sherman, D.H.,Aldrich, C.C.,Smith, J.L.
Structural Basis of Polyketide Synthase O-Methylation.
ACS Chem. Biol., 13:3221-3228, 2018

PubMed Abstract: Modular type I polyketide synthases (PKSs) produce some of the most chemically complex metabolites in nature through a series of multienzyme modules. Each module contains a variety of catalytic domains to selectively tailor the growing molecule. PKS O-methyltransferases ( O-MTs) are predicted to methylate β-hydroxyl or β-keto groups, but their activity and structure have not been reported. We determined the domain boundaries and characterized the catalytic activity and structure of the StiD and StiE O-MTs, which methylate opposite β-hydroxyl stereocenters in the myxobacterial stigmatellin biosynthetic pathway. Substrate stereospecificity was demonstrated for the StiD O-MT. Key catalytic residues were identified in the crystal structures and investigated in StiE O-MT via site-directed mutagenesis and further validated with the cyanobacterial CurL O-MT from the curacin biosynthetic pathway. Initial structural and biochemical analysis of PKS O-MTs supplies a new chemoenzymatic tool, with the unique ability to selectively modify hydroxyl groups during polyketide biosynthesis.

PubMed: 30489068
DOI: 10.1021/acschembio.8b00687

Experimental method

X-RAY DIFFRACTION (1.42 Å)