3ri3 | pdb_00003ri3

Actinorhodin Polyketide Ketoreductase Mutant P94L bound to NADPH and the Inhibitor Emodin

spinqualitylabelsall models 3ri3, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ri3 is a 2 chain structure with sequence from "actinomyces_coelicolor"_(muller_1908)_lieske_1921 "actinomyces coelicolor" (muller 1908) lieske 1921. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EMO, NDP Gene: actIII, SCBAC28G1.12c, SCO5086 ("Actinomyces coelicolor" (Muller 1908) Lieske 1921) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Type II polyketides include antibiotics such as tetracycline and chemotherapeutics such as daunorubicin. Type II polyketides are biosynthesized by the type II polyketide synthase (PKS) that consists of 5-10 stand-alone domains. In many type II PKSs, the type II ketoreductase (KR) specifically reduces the C9-carbonyl group. How the type II KR achieves such a high regiospecificity and the nature of stereospecificity are not well understood. Sequence alignment of KRs led to a hypothesis that a well-conserved 94-XGG-96 motif may be involved in controlling the stereochemistry. The stereospecificity of single-, double-, and triple-mutant combinations of P94L, G95D, and G96D were analyzed in vitro and in vivo for the actinorhodin KR (actKR). The P94L mutation is sufficient to change the stereospecificity of actKR. Binary and ternary crystal structures of both wild-type and P94L actKR were determined. Together with assay results, docking simulations, and cocrystal structures, a model for stereochemical control is presented herein that elucidates how type II polyketides are introduced into the substrate pocket such that the C9-carbonyl can be reduced with high regio- and stereospecificities. The molecular features of actKR important for regio- and stereospecificities can potentially be applied in biosynthesizing new polyketides via protein engineering that rationally controls polyketide keto reduction. Structural and Biochemical Analyses of Regio- and Stereospecificities Observed in a Type II Polyketide Ketoreductase.,Javidpour P, Korman TP, Shakya G, Tsai SC Biochemistry. 2011 May 31;50(21):4638-49. Epub 2011 May 4. PMID:21506596 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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