2q6o
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(New page: 200px<br /><applet load="2q6o" size="350" color="white" frame="true" align="right" spinBox="true" caption="2q6o, resolution 2.00Å" /> '''SalL-Y70T with SAM a...)
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Revision as of 09:02, 23 January 2008
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SalL-Y70T with SAM and Cl
Overview
Halogen atom incorporation into a scaffold of bioactive compounds often, amplifies biological activity, as is the case for the anticancer agent, salinosporamide A (1), a chlorinated natural product from the marine, bacterium Salinispora tropica. Significant effort in understanding, enzymatic chlorination shows that oxidative routes predominate to form, reactive electrophilic or radical chlorine species. Here we report the, genetic, biochemical and structural characterization of the chlorinase, SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to, generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) in a rarely, observed nucleophilic substitution strategy analogous to that of, Streptomyces cattleya fluorinase. Further metabolic tailoring produces a, halogenated polyketide synthase substrate specific for salinosporamide A, biosynthesis. SalL also accepts bromide and iodide as substrates, but not, fluoride. High-resolution crystal structures of SalL and active site, mutants complexed with substrates and products support the S(N)2, nucleophilic substitution mechanism and further illuminate halide, specificity in this newly discovered halogenase family.
About this Structure
2Q6O is a Single protein structure of sequence from Bacteria with and as ligands. Full crystallographic information is available from OCA.
Reference
Discovery and characterization of a marine bacterial SAM-dependent chlorinase., Eustaquio AS, Pojer F, Noel JP, Moore BS, Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:18059261
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