1q7t
From Proteopedia
(New page: 200px<br /><applet load="1q7t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q7t, resolution 1.90Å" /> '''Rv1170 (MshB) from M...) |
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| - | [[Image:1q7t.gif|left|200px]]<br /><applet load="1q7t" size=" | + | [[Image:1q7t.gif|left|200px]]<br /><applet load="1q7t" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q7t, resolution 1.90Å" /> | caption="1q7t, resolution 1.90Å" /> | ||
'''Rv1170 (MshB) from Mycobacterium tuberculosis'''<br /> | '''Rv1170 (MshB) from Mycobacterium tuberculosis'''<br /> | ||
==Overview== | ==Overview== | ||
| - | All living species require protection against the damaging effects of the | + | All living species require protection against the damaging effects of the reactive oxygen species that are a natural by-product of aerobic life. In most organisms, glutathione is a critical component of these defences, maintaining a reducing environment inside cells. Some bacteria, however, including pathogenic mycobacteria, use an alternative low molecular mass thiol compound called mycothiol (MSH) for this purpose. Enzymes that synthesize MSH are attractive candidates for the design of novel anti-TB drugs because of the importance of MSH for mycobacterial life and the absence of such enzymes in humans. We have determined the three-dimensional structure of MshB (Rv1170), a metal-dependent deacetylase from Mycobacterium tuberculosis that catalyses the second step in MSH biosynthesis. The structure, determined at 1.9A resolution by X-ray crystallography (R=19.0%, R(free)=21.4%), reveals an alpha/beta fold in which helices pack against a seven-stranded mostly parallel beta-sheet. Large loops emanating from the C termini of the beta-strands enclose a deep cavity, which is the location of the putative active site. At the bottom of this cavity is a metal-binding site associated with a sequence motif AHPDDE that is invariant in all homologues. An adventitiously bound beta-octylglucoside molecule, used in crystallization, enables us to model the binding of the true substrate and propose a metal-dependent mechanistic model for deacetylation. Sequence comparisons indicate that MshB is representative of a wider family of enzymes that act on substituted N-acetylglucosamine residues, including a deacetylase involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors in eukaryotes. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q7T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with BOG and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1Q7T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=BOG:'>BOG</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q7T OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baker, E | + | [[Category: Baker, E N.]] |
[[Category: Knijff, R.]] | [[Category: Knijff, R.]] | ||
| - | [[Category: McCarthy, A | + | [[Category: McCarthy, A A.]] |
| - | [[Category: Peterson, N | + | [[Category: Peterson, N A.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: BOG]] | [[Category: BOG]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| Line 27: | Line 27: | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:48 2008'' |
Revision as of 12:36, 21 February 2008
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Rv1170 (MshB) from Mycobacterium tuberculosis
Overview
All living species require protection against the damaging effects of the reactive oxygen species that are a natural by-product of aerobic life. In most organisms, glutathione is a critical component of these defences, maintaining a reducing environment inside cells. Some bacteria, however, including pathogenic mycobacteria, use an alternative low molecular mass thiol compound called mycothiol (MSH) for this purpose. Enzymes that synthesize MSH are attractive candidates for the design of novel anti-TB drugs because of the importance of MSH for mycobacterial life and the absence of such enzymes in humans. We have determined the three-dimensional structure of MshB (Rv1170), a metal-dependent deacetylase from Mycobacterium tuberculosis that catalyses the second step in MSH biosynthesis. The structure, determined at 1.9A resolution by X-ray crystallography (R=19.0%, R(free)=21.4%), reveals an alpha/beta fold in which helices pack against a seven-stranded mostly parallel beta-sheet. Large loops emanating from the C termini of the beta-strands enclose a deep cavity, which is the location of the putative active site. At the bottom of this cavity is a metal-binding site associated with a sequence motif AHPDDE that is invariant in all homologues. An adventitiously bound beta-octylglucoside molecule, used in crystallization, enables us to model the binding of the true substrate and propose a metal-dependent mechanistic model for deacetylation. Sequence comparisons indicate that MshB is representative of a wider family of enzymes that act on substituted N-acetylglucosamine residues, including a deacetylase involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors in eukaryotes.
About this Structure
1Q7T is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of MshB from Mycobacterium tuberculosis, a deacetylase involved in mycothiol biosynthesis., McCarthy AA, Peterson NA, Knijff R, Baker EN, J Mol Biol. 2004 Jan 23;335(4):1131-41. PMID:14698305
Page seeded by OCA on Thu Feb 21 14:36:48 2008
Categories: Mycobacterium tuberculosis | Single protein | Baker, E N. | Knijff, R. | McCarthy, A A. | Peterson, N A. | TBSGC, TB Structural Genomics Consortium. | BOG | SO4 | Modified rossmann fold | Protein structure initiative | Psi | Structural genomics | Tb structural genomics consortium | Tbsgc
