2rhr | pdb_00002rhr

P94L actinorhodin ketordeuctase mutant, with NADPH and Inhibitor Emodin

spinqualitylabelsall models 2rhr, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2rhr 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 Related: 1x7h, 1x7g, 2rh4, 2rhc Gene: actIII ("Actinomyces coelicolor" (Muller 1908) Lieske 1921) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Type II polyketides are a class of natural products that include pharmaceutically important aromatic compounds such as the antibiotic tetracycline and antitumor compound doxorubicin. The type II polyketide synthase (PKS) is a complex consisting of 5-10 standalone domains homologous to fatty acid synthase (FAS). Polyketide ketoreductase (KR) provides regio- and stereochemical diversity during the reduction. How the type II polyketide KR specifically reduces only the C9 carbonyl group is not well understood. The cocrystal structures of actinorhodin polyketide ketoreductase (actKR) bound with NADPH or NADP+ and the inhibitor emodin were solved with the wild type and P94L mutant of actKR, revealing the first observation of a bent p-quinone in an enzyme active site. Molecular dynamics simulation help explain the origin of the bent geometry. Extensive screening for in vitro substrates shows that unlike FAS KR, the actKR prefers bicyclic substrates. Inhibition kinetics indicate that actKR follows an ordered Bi Bi mechanism. Together with docking simulations that identified a potential phosphopantetheine binding groove, the structural and functional studies reveal that the C9 specificity is a result of active site geometry and substrate ring constraints. The results lay the foundation for the design of novel aromatic polyketide natural products with different reduction patterns. Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase.,Korman TP, Tan YH, Wong J, Luo R, Tsai SC Biochemistry. 2008 Feb 19;47(7):1837-47. Epub 2008 Jan 19. PMID:18205400 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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