1x7g
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(New page: 200px<br /><applet load="1x7g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x7g, resolution 2.30Å" /> '''Actinorhodin Polyket...)
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Revision as of 03:45, 21 November 2007
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Actinorhodin Polyketide Ketoreductase, act KR, with NADP bound
Overview
Aromatic polyketides are a class of natural products that include many, pharmaceutically important aromatic compounds. Understanding the structure, and function of PKS will provide clues to the molecular basis of, polyketide biosynthesis specificity. Polyketide chain reduction by, ketoreductase (KR) provides regio- and stereochemical diversity. Two, cocrystal structures of actinorhodin polyketide ketoreductase (act KR), were solved to 2.3 A with either the cofactor NADP(+) or NADPH bound. The, monomer fold is a highly conserved Rossmann fold. Subtle differences, between structures of act KR and fatty acid KRs fine-tune the tetramer, interface and substrate binding pocket. Comparisons of the NADP(+)- and, NADPH-bound structures indicate that the alpha6-alpha7 loop region is, highly flexible. The intricate proton-relay network in the active site, leads to the proposed catalytic mechanism involving four waters, NADPH, and the active site tetrad Asn114-Ser144-Tyr157-Lys161. Acyl carrier, protein and substrate docking models shed light on the molecular basis of, KR regio- and stereoselectivity, as well as the differences between, aromatic polyketide and fatty acid biosyntheses. Sequence comparison, indicates that the above features are highly conserved among aromatic, polyketide KRs. The structures of act KR provide an important step toward, understanding aromatic PKS and will enhance our ability to design novel, aromatic polyketide natural products with different reduction patterns.
About this Structure
1X7G is a Single protein structure of sequence from Streptomyces coelicolor with NAP as ligand. Full crystallographic information is available from OCA.
Reference
Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity., Korman TP, Hill JA, Vu TN, Tsai SC, Biochemistry. 2004 Nov 23;43(46):14529-38. PMID:15544323
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