1W4Z

Structure of actinorhodin polyketide (actIII) Reductase

Summary for 1W4Z

• Entry DOI: 10.2210/pdb1w4z/pdb
• Descriptor: KETOACYL REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, FORMIC ACID, ... (4 entities in total)
• Functional Keywords: type ii polyketide synthesis, ketoreductase, sdr, acp binding, antibiotic biosynthesis
• Biological source: STREPTOMYCES COELICOLOR
• Total number of polymer chains: 2
• Total formula weight: 60829.76

Authors

Hadfield, A.T.,Limpkin, C.,Teartasin, W.,Simpson, T.J.,Crosby, J.,Crump, M.P. (deposition date: 2004-08-03, release date: 2004-12-10, Last modification date: 2023-12-13)

Primary citation

Hadfield, A.T.,Limpkin, C.,Teartasin, W.,Simpson, T.J.,Crosby, J.,Crump, M.P.
The Crystal Structure of the Actiii Actinorhodin Polyketide Reductase; Proposed Mechanism for Acp and Polyketide Binding
Structure, 12:1865-, 2004

PubMed Abstract: We have determined the 2.5 angstroms crystal structure of an active, tetrameric Streptomyces coelicolor type II polyketide ketoreductase (actIII) with its bound cofactor, NADP+. This structure shows a Rossman dinucleotide binding fold characteristic of SDR enzymes. Of two subunits in the crystallographic asymmetric unit, one is closed around the active site. Formate is observed in the open subunit, indicating possible carbonyl binding sites of the polyketide intermediate. Unlike previous models we observe crystal contacts that may mimic the KR-ACP interactions that may drive active site opening. Based on these observations, we have constructed a model for ACP and polyketide binding. We propose that binding of ACP triggers a conformational change from the closed to the open, active form of the enzyme. The polyketide chain enters the active site and reduction occurs. The model also suggests a general mechanism for ACP recognition which is applicable to a range of protein families.

PubMed: 15458634
DOI: 10.1016/J.STR.2004.08.002

Experimental method

X-RAY DIFFRACTION (2.5 Å)