2ixc: Difference between revisions

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[[Image:2ixc.gif|left|200px]]<br />
<applet load="2ixc" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2ixc, resolution 1.79&Aring;" />
'''RMLC M. TUBERCULOSIS WITH DTDP-RHAMNOSE'''<br />


==Overview==
==RmlC M. tuberculosis with dTDP-rhamnose==
The striking feature of carbohydrates is their constitutional, conformational and configurational diversity. Biology has harnessed this, diversity and manipulates carbohydrate residues in a variety of ways, one, of which is epimerization. RmlC 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. RmlC is the third enzyme of the rhamnose, pathway, and represents a validated anti-bacterial drug target. Although, several structures of the enzyme have been reported, the mechanism and the, nature of the intermediates have remained obscure. Despite its relatively, small size (22 kDa), RmlC catalyzes four stereospecific proton transfers, and the substrate undergoes a major conformational change during the, course of ... [[http://ispc.weizmann.ac.il/pmbin/getpm?17046787 (full description)]]
<StructureSection load='2ixc' size='340' side='right'caption='[[2ixc]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ixc]] is a 4 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=2IXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IXC 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]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRH:2-DEOXY-THYMIDINE-BETA-L-RHAMNOSE'>TRH</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=2ixc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ixc OCA], [https://pdbe.org/2ixc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ixc RCSB], [https://www.ebi.ac.uk/pdbsum/2ixc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ixc 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/ix/2ixc_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=2ixc ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The striking feature of carbohydrates is their constitutional, conformational and configurational diversity. Biology has harnessed this diversity and manipulates carbohydrate residues in a variety of ways, one of which is epimerization. RmlC 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. RmlC is the third enzyme of the rhamnose pathway, and represents a validated anti-bacterial drug target. Although several structures of the enzyme have been reported, the mechanism and the nature of the intermediates have remained obscure. Despite its relatively small size (22 kDa), RmlC catalyzes four stereospecific proton transfers and the substrate undergoes a major conformational change during the course of the transformation. Here we report the structure of RmlC from several organisms in complex with product and product mimics. We have probed site-directed mutants by assay and by deuterium exchange. The combination of structural and biochemical data has allowed us to assign key residues and identify the conformation of the carbohydrate during turnover. Clear knowledge of the chemical structure of RmlC reaction intermediates may offer new opportunities for rational drug design.


==About this Structure==
RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation.,Dong C, Major LL, Srikannathasan V, Errey JC, Giraud MF, Lam JS, Graninger M, Messner P, McNeil MR, Field RA, Whitfield C, Naismith JH J Mol Biol. 2007 Jan 5;365(1):146-59. Epub 2006 Sep 29. PMID:17046787<ref>PMID:17046787</ref>
2IXC 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 TRH as [[http://en.wikipedia.org/wiki/ligand ligand]]. 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]]. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IXC OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
RmlC, a C3' and C5' carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation., Dong C, Major LL, Srikannathasan V, Errey JC, Giraud MF, Lam JS, Graninger M, Messner P, McNeil MR, Field RA, Whitfield C, Naismith JH, J Mol Biol. 2007 Jan 5;365(1):146-59. Epub 2006 Sep 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17046787 17046787]
</div>
<div class="pdbe-citations 2ixc" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[RmlC|RmlC]]
== References ==
<references/>
__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: TRH]]
[[Category: epimerase]]
[[Category: epimerise]]
[[Category: epimerize]]
[[Category: isomerase]]
[[Category: lipopolysaccharide biosynthesis]]
 
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