2q6l

SalL double mutant Y70T/G131S with CLDA and L-MET

spinqualitylabelsall models 2q6l, resolution 2.72Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q6l is a 1 chain structure with sequence from Salinispora tropica CNB-440. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.72Å Ligands: 5CD, MET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SALL_SALTO Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride. 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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