1jwx
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(New page: 200px<br /><applet load="1jwx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jwx, resolution 1.63Å" /> '''Chalcone Synthase--F...)
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Revision as of 16:31, 20 November 2007
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Chalcone Synthase--F215S mutant
Overview
Type III polyketide synthases (PKS) generate an array of natural products, by condensing multiple acetyl units derived from malonyl-CoA to, thioester-linked starter molecules covalently bound in the PKS active, site. One strategy adopted by Nature for increasing the functional, diversity of these biosynthetic enzymes involves modifying polyketide, assembly by altering the preference for starter molecules. Chalcone, synthase (CHS) is a ubiquitous plant PKS and the first type III PKS, described functionally and structurally. Guided by the three-dimensional, structure of CHS, Phe-215 and Phe-265, which are situated at the active, site entrance, were targeted for site-directed mutagenesis to diversify, CHS activity. The resulting mutants were screened against a panel of, aliphatic and aromatic CoA-linked starter molecules to evaluate the degree, of starter molecule specificity in CHS. Although wild-type CHS accepts a, number of natural CoA thioesters, it does not use N-methylanthraniloyl-CoA, as a substrate. Substitution of Phe-215 by serine yields a CHS mutant that, preferentially accepts this CoA-thioester substrate to generate a novel, alkaloid, namely N-methylanthraniloyltriacetic acid lactone. These results, demonstrate that a point mutation in CHS dramatically shifts the molecular, selectivity of this enzyme. This structure-based approach to metabolic, redesign represents an initial step toward tailoring the biosynthetic, activity of plant type III PKS.
About this Structure
1JWX is a Single protein structure of sequence from Medicago sativa. Active as Naringenin-chalcone synthase, with EC number 2.3.1.74 Full crystallographic information is available from OCA.
Reference
Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity., Jez JM, Bowman ME, Noel JP, Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5319-24. PMID:11959984
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