1pm7: Difference between revisions

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New page: left|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="450" 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==
==RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.==
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.
<StructureSection load='1pm7' size='340' side='right'caption='[[1pm7]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pm7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PM7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PM7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pm7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pm7 OCA], [https://pdbe.org/1pm7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pm7 RCSB], [https://www.ebi.ac.uk/pdbsum/1pm7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pm7 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RMLC_MYCTU RMLC_MYCTU] Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage.<ref>PMID:16472764</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/1pm7_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pm7 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PM7 OCA].
*[[RmlC|RmlC]]
 
== References ==
==Reference==
<references/>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12951098 12951098]
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Dong C]]
[[Category: dTDP-4-dehydrorhamnose 3,5-epimerase]]
[[Category: Naismith JH]]
[[Category: Dong, C.]]
[[Category: Naismith, J.H.]]
[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
[[Category: ACT]]
[[Category: GOL]]
[[Category: beta barrel]]
[[Category: main beta sheet structure]]
[[Category: protein structure initiative]]
[[Category: psi]]
[[Category: rmlc]]
[[Category: structural genomics]]
[[Category: tb structural genomics consortium]]
[[Category: tbsgc]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:41:31 2007''

Latest revision as of 11:09, 14 February 2024

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

Structural highlights

1pm7 is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RMLC_MYCTU Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Li W, Xin Y, McNeil MR, Ma Y. rmlB and rmlC genes are essential for growth of mycobacteria. Biochem Biophys Res Commun. 2006 Mar 31;342(1):170-8. Epub 2006 Feb 3. PMID:16472764 doi:http://dx.doi.org/10.1016/j.bbrc.2006.01.130

1pm7, resolution 2.20Å

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