2Q6O

SalL-Y70T with SAM and Cl

Summary for 2Q6O

• Entry DOI: 10.2210/pdb2q6o/pdb
• Related: 2Q6I 2Q6K 2Q6L
• Descriptor: Hypothetical Protein, CHLORIDE ION, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: chlorinase, y70t mutant sam and cl complex, biosynthetic protein
• Biological source: Salinispora tropica
• Total number of polymer chains: 2
• Total formula weight: 61094.15

Authors

Noel, J.P.,Pojer, F. (deposition date: 2007-06-05, release date: 2007-12-11, Last modification date: 2024-02-21)

Primary citation

Eustaquio, A.S.,Pojer, F.,Noel, J.P.,Moore, B.S.
Discovery and characterization of a marine bacterial SAM-dependent chlorinase
Nat.Chem.Biol., 4:69-74, 2008

PubMed Abstract: 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.

PubMed: 18059261
DOI: 10.1038/nchembio.2007.56

Experimental method

X-RAY DIFFRACTION (2 Å)