1ME5

Crystal Structure of Mycobacterium Tuberculosis Alkylperoxidase AhpD H132Q Mutant

1ME5 の概要

• エントリーDOI: 10.2210/pdb1me5/pdb
• 関連するPDBエントリー: 1LW1
• 分子名称: ALKYLHYDROPEROXIDASE D (2 entities in total)
• 機能のキーワード: trimer, alpha helical, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 56374.51

構造登録者

Nunn, C.M.,Djordjevic, S.,Ortiz de Montellano, P.R. (登録日: 2002-08-08, 公開日: 2002-09-11, 最終更新日: 2024-02-14)

主引用文献

Koshkin, A.,Nunn, C.M.,Djordjevic, S.,Ortiz de Montellano, P.R.
The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics.
J.Biol.Chem., 278:29502-29508, 2003

PubMed Abstract: AhpD, a protein with two cysteine residues, is required for physiological reduction of the Mycobacterium tuberculosis alkylhydroperoxidase AhpC. AhpD also has an alkylhydroperoxidase activity of its own. The AhpC/AhpD system provides critical antioxidant protection, particularly in the absence of the catalase-peroxidase KatG, which is suppressed in most isoniazid-resistant strains. Based on the crystal structure, we proposed recently a catalytic mechanism for AhpD involving a proton relay in which the Glu118 carboxylate group, via His137 and a water molecule, deprotonates the catalytic residue Cys133 (Nunn, C. M., Djordjevic, S., Hillas, P. J., Nishida, C., and Ortiz de Montellano, P. R. (2002) J. Biol. Chem. 277, 20033-20040). A possible role for His132 in subsequent formation of the Cys133-Cys130 disulfide bond was also noted. To test this proposed mechanism, we have expressed the H137F, H137Q, H132F, H132Q, E118F, E118Q, C133S, and C130S mutants of AhpD, determined the crystal structures of the H137F and H132Q mutants, estimated the pKa values of the cysteine residues, and defined the kinetic properties of the mutant proteins. The collective results strongly support the proposed catalytic mechanism for AhpD.

PubMed: 12761216
DOI: 10.1074/jbc.M303747200

実験手法

X-RAY DIFFRACTION (2.4 Å)