1Q74

The Crystal Structure of 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB)

1Q74 の概要

• エントリーDOI: 10.2210/pdb1q74/pdb
• 分子名称: 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB), ZINC ION, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (4 entities in total)
• 機能のキーワード: rossmann fold, zinc aminohydrolase, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 127724.99

構造登録者

Maynes, J.T.,Garen, C.,Cherney, M.M.,Newton, G.,Arad, D.,Av-Gay, Y.,Fahey, R.C.,James, M.N.,TB Structural Genomics Consortium (TBSGC) (登録日: 2003-08-15, 公開日: 2003-12-02, 最終更新日: 2024-02-21)

主引用文献

Maynes, J.T.,Garen, C.,Cherney, M.M.,Newton, G.,Arad, D.,Av-Gay, Y.,Fahey, R.C.,James, M.N.
The Crystal Structure of 1-D-myo-Inositol 2-Acetamido-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB) from Mycobacterium tuberculosis Reveals a Zinc Hydrolase with a Lactate Dehydrogenase Fold.
J.Biol.Chem., 278:47166-47170, 2003

PubMed Abstract: Mycothiol (1-D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside, MSH or AcCys-GlcN-inositol (Ins)) is the major reducing agent in actinomycetes, including Mycobacterium tuberculosis. The biosynthesis of MSH involves a deacetylase that removes the acetyl group from the precursor GlcNAc-Ins to yield GlcN-Ins. The deacetylase (MshB) corresponds to Rv1170 of M. tuberculosis with a molecular mass of 33,400 Da. MshB is a Zn2+ metalloprotein, and the deacetylase activity is completely dependent on the presence of a divalent metal cation. We have determined the x-ray crystallographic structure of MshB, which reveals a protein that folds in a manner resembling lactate dehydrogenase in the N-terminal domain and a C-terminal domain consisting of two beta-sheets and two alpha-helices. The zinc binding site is in the N-terminal domain occupying a position equivalent to that of the NAD+ co-factor of lactate dehydrogenase. The Zn2+ is 5 coordinate with 3 residues from MshB (His-13, Asp-16, His-147) and two water molecules. One water would be displaced upon binding of substrate (GlcNAc-Ins); the other is proposed as the nucleophilic water assisted by the general base carboxylate of Asp-15. In addition to the Zn2+ providing electrophilic assistance in the hydrolysis, His-144 imidazole could form a hydrogen bond to the oxyanion of the tetrahedral intermediate. The extensive sequence identity of MshB, the deacetylase, with mycothiol S-conjugate amidase, an amide hydrolase that mediates detoxification of mycothiol S-conjugate xenobiotics, has allowed us to construct a faithful model of the catalytic domain of mycothiol S-conjugate amidase based on the structure of MshB.

PubMed: 12958317
DOI: 10.1074/jbc.M308914200

実験手法

X-RAY DIFFRACTION (1.7 Å)