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| [[Image:2q6o.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2q6o| PDB=2q6o | SCENE= }} | | {{STRUCTURE_2q6o| PDB=2q6o | SCENE= }} |
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| '''SalL-Y70T with SAM and Cl'''
| | ===SalL-Y70T with SAM and Cl=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18059261}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18059261 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18059261}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Chlorinase]] | | [[Category: Chlorinase]] |
| [[Category: Y70t mutant sam and cl complex]] | | [[Category: Y70t mutant sam and cl complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:27:00 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:55:58 2008'' |
