1Q74
The Crystal Structure of 1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside Deacetylase (MshB)
Summary for 1Q74
| Entry DOI | 10.2210/pdb1q74/pdb |
| Descriptor | 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) |
| Functional Keywords | rossmann fold, zinc aminohydrolase, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, hydrolase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 4 |
| Total formula weight | 127724.99 |
| Authors | 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) (deposition date: 2003-08-15, release date: 2003-12-02, Last modification date: 2024-02-21) |
| Primary citation | 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 Cited by 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: 12958317DOI: 10.1074/jbc.M308914200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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