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[[Image:2ntn.gif|left|200px]]<br /><applet load="2ntn" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2ntn, resolution 2.30&Aring;" />
'''Crystal structure of MabA-C60V/G139A/S144L'''<br />


==Overview==
==Crystal structure of MabA-C60V/G139A/S144L==
The MabA protein from Mycobacterium tuberculosis is a validated drug, target. Previous structural studies of this protein showed dynamic, behaviour in the catalytic site and described motion between an open, ;active' holo form (with NADP) and a closed ;inactive' apo form (without, NADP). Here, a mutation (G139A) is reported that leads to complete protein, inactivation and freezes the catalytic site into its closed form, even in, the presence of the cofactor. This observation suggests a new way to, develop anti-MabA drugs via protein stabilization of the ;inactive' form.
<StructureSection load='2ntn' size='340' side='right'caption='[[2ntn]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ntn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NTN 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]] 2.3&#8491;</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=2ntn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ntn OCA], [https://pdbe.org/2ntn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ntn RCSB], [https://www.ebi.ac.uk/pdbsum/2ntn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ntn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MABA_MYCTU MABA_MYCTU] Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis (PubMed:11932442). Catalyzes the NADPH-dependent reduction of beta-ketoacyl derivatives, the second step of the FAS-II elongation cycle (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153, PubMed:19685079). May preferentially metabolize long-chain substrates (C8-C20) (PubMed:11932442). Can use CoA derivatives as substrates in vitro (PubMed:9802011, PubMed:11932442, PubMed:17059223, PubMed:18155153).<ref>PMID:11932442</ref> <ref>PMID:17059223</ref> <ref>PMID:18155153</ref> <ref>PMID:19685079</ref> <ref>PMID:9802011</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/nt/2ntn_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=2ntn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The MabA protein from Mycobacterium tuberculosis is a validated drug target. Previous structural studies of this protein showed dynamic behaviour in the catalytic site and described motion between an open 'active' holo form (with NADP) and a closed 'inactive' apo form (without NADP). Here, a mutation (G139A) is reported that leads to complete protein inactivation and freezes the catalytic site into its closed form, even in the presence of the cofactor. This observation suggests a new way to develop anti-MabA drugs via protein stabilization of the 'inactive' form.


==About this Structure==
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies.,Poncet-Montange G, Ducasse-Cabanot S, Quemard A, Labesse G, Cohen-Gonsaud M Acta Crystallogr D Biol Crystallogr. 2007 Aug;63(Pt 8):923-5. Epub 2007, Jul 17. PMID:17642518<ref>PMID:17642518</ref>
2NTN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Active as [http://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.100 1.1.1.100] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NTN OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies., Poncet-Montange G, Ducasse-Cabanot S, Quemard A, Labesse G, Cohen-Gonsaud M, Acta Crystallogr D Biol Crystallogr. 2007 Aug;63(Pt 8):923-5. Epub 2007, Jul 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17642518 17642518]
</div>
[[Category: 3-oxoacyl-[acyl-carrier-protein] reductase]]
<div class="pdbe-citations 2ntn" style="background-color:#fffaf0;"></div>
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Cohen-Gonsaud, M.]]
[[Category: Ducasse-Cabanot, S.]]
[[Category: Labesse, G.]]
[[Category: Poncet-Montange, G.]]
[[Category: Quemard, A.]]
[[Category: beta-ketoacyl acp reductase]]
[[Category: inactive]]
[[Category: oxidoreductase]]
[[Category: sdr]]


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:07:09 2008''
==See Also==
*[[Beta-ketoacyl carrier protein reductase 3D structures|Beta-ketoacyl carrier protein reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Cohen-Gonsaud M]]
[[Category: Ducasse-Cabanot S]]
[[Category: Labesse G]]
[[Category: Poncet-Montange G]]
[[Category: Quemard A]]

Latest revision as of 08:55, 25 October 2023

Crystal structure of MabA-C60V/G139A/S144L

2ntn, resolution 2.30Å

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