1pm7
From Proteopedia
(New page: 200px<br /><applet load="1pm7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pm7, resolution 2.20Å" /> '''RmlC (dTDP-6-DEOXY-D...) |
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| - | [[Image:1pm7.gif|left|200px]]<br /><applet load="1pm7" size=" | + | [[Image:1pm7.gif|left|200px]]<br /><applet load="1pm7" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pm7, resolution 2.20Å" /> | caption="1pm7, resolution 2.20Å" /> | ||
'''RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.'''<br /> | '''RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The emergence of multi-drug resistant tuberculosis, coupled with the | + | The emergence of multi-drug resistant tuberculosis, coupled with the increasing overlap of the AIDS and tuberculosis pandemics has brought tuberculosis to the forefront as a major worldwide health concern. In an attempt to find new inhibitors of the enzymes in the essential rhamnose biosynthetic pathway, a virtual library of 2,3,5 trisubstituted-4-thiazolidinones was created. These compounds were then docked into the active site cavity of 6'hydroxyl; dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase (RmlC) from Mycobacterium tuberculosis. The resulting docked conformations were consensus scored and the top 5% were slated for synthesis. Thus far, 94 compounds have been successfully synthesized and initially tested. Of those, 30 (32%) have > or =50% inhibitory activity (at 20 microM) in the coupled rhamnose synthetic assay with seven of the 30 also having modest activity against whole-cell M. tuberculosis. |
==About this Structure== | ==About this Structure== | ||
| - | 1PM7 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 ACT and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dTDP-4-dehydrorhamnose_3,5-epimerase dTDP-4-dehydrorhamnose 3,5-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.13 5.1.3.13] Full crystallographic information is available from [http:// | + | 1PM7 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=ACT:'>ACT</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dTDP-4-dehydrorhamnose_3,5-epimerase dTDP-4-dehydrorhamnose 3,5-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.13 5.1.3.13] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PM7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: dTDP-4-dehydrorhamnose 3,5-epimerase]] | [[Category: dTDP-4-dehydrorhamnose 3,5-epimerase]] | ||
[[Category: Dong, C.]] | [[Category: Dong, C.]] | ||
| - | [[Category: Naismith, J | + | [[Category: Naismith, J H.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:12 2008'' |
Revision as of 12:30, 21 February 2008
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RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.
Overview
The emergence of multi-drug resistant tuberculosis, coupled with the increasing overlap of the AIDS and tuberculosis pandemics has brought tuberculosis to the forefront as a major worldwide health concern. In an attempt to find new inhibitors of the enzymes in the essential rhamnose biosynthetic pathway, a virtual library of 2,3,5 trisubstituted-4-thiazolidinones was created. These compounds were then docked into the active site cavity of 6'hydroxyl; dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase (RmlC) from Mycobacterium tuberculosis. The resulting docked conformations were consensus scored and the top 5% were slated for synthesis. Thus far, 94 compounds have been successfully synthesized and initially tested. Of those, 30 (32%) have > or =50% inhibitory activity (at 20 microM) in the coupled rhamnose synthetic assay with seven of the 30 also having modest activity against whole-cell M. tuberculosis.
About this Structure
1PM7 is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as dTDP-4-dehydrorhamnose 3,5-epimerase, with EC number 5.1.3.13 Full crystallographic information is available from OCA.
Reference
Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis., Babaoglu K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE, Bioorg Med Chem Lett. 2003 Oct 6;13(19):3227-30. PMID:12951098
Page seeded by OCA on Thu Feb 21 14:30:12 2008
Categories: Mycobacterium tuberculosis | Single protein | DTDP-4-dehydrorhamnose 3,5-epimerase | Dong, C. | Naismith, J H. | TBSGC, TB Structural Genomics Consortium. | ACT | GOL | Beta barrel | Main beta sheet structure | Protein structure initiative | Psi | Rmlc | Structural genomics | Tb structural genomics consortium | Tbsgc
