1pm7: Difference between revisions

Revision as of 15:30, 21 February 2008

RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.

OverviewOverview

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 StructureAbout 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.

ReferenceReference

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1pm7.gif|left|200px]]<br /><applet load="1pm7" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1pm7.gif|left|200px]]<br /><applet load="1pm7" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1pm7, resolution 2.20&Aring;" />
 '''RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.'''<br />
 ==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 &gt;, 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.
+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 &gt; 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==
-PM7 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PM7 OCA].
+PM7 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==
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 [[Category: dTDP-4-dehydrorhamnose 3,5-epimerase]]
 [[Category: Dong, C.]]
-[[Category: Naismith, J.H.]]
+[[Category: Naismith, J H.]]
-[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
+[[Category: TBSGC, TB Structural Genomics Consortium.]]
 [[Category: ACT]]
 [[Category: GOL]]
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 [[Category: tbsgc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:41:31 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:12 2008''