4DBZ: Crystal Structure Of V151l Actinorhodin Polyketide Ketoreductase With Nadph

In the actinorhodin type II polyketide synthase, the first polyketide modification is a regiospecific C9-carbonyl reduction, catalyzed by the ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif as a determinant of stereospecificity. The molecular basis for reduction regiospecificity is, however, not well understood. In this study, we examined the activities of 20 actKR mutants through a combination of kinetic studies, PKS reconstitution, and structural analyses. Residues have been identified that are necessary for substrate interaction, and these observations have suggested a structural model for this reaction. Polyketides dock at the KR surface and are steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR before C9-ketoreduction can occur. These molecular features can potentially serve as engineering targets for the biosynthesis of novel, reduced polyketides.
PDB ID: 4DBZDownload
MMDB ID: 106689
PDB Deposition Date: 2012/1/16
Updated in MMDB: 2013/11
Experimental Method:
x-ray diffraction
Resolution: 2.64  Å
Source Organism:
Similar Structures:
Biological Unit for 4DBZ: tetrameric; determined by author and by software (PISA)
Molecular Components in 4DBZ
Label Count Molecule
Proteins (4 molecules)
Ketoacyl Reductase(Gene symbol: SCO5086)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB