2Q6L

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

2Q6L の概要

• エントリーDOI: 10.2210/pdb2q6l/pdb
• 関連するPDBエントリー: 2Q6I 2Q6K 2Q6O
• 分子名称: Hypothetical protein, 5'-CHLORO-5'-DEOXYADENOSINE, METHIONINE, ... (4 entities in total)
• 機能のキーワード: chlorinase, double mutant complex with clda and l-met, biosynthetic protein
• 由来する生物種: Salinispora tropica
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30692.21

構造登録者

Pojer, F.,Noel, J.P. (登録日: 2007-06-05, 公開日: 2007-12-11, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.72 Å)