1u9n

From Proteopedia

(Difference between revisions)

Revision as of 08:37, 21 March 2018

Crystal structure of the transcriptional regulator EthR in a ligand bound conformation opens therapeutic perspectives against tuberculosis and leprosy

Structural highlights

1u9n is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	1u9o
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).^[1] ^[2]

Evolutionary Conservation

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

Publication Abstract from PubMed

Mycobacterium tuberculosis EthR is a repressor of ethA, a gene encoding a mono-oxygenase required for the activation of the prodrug ethionamide. Here we describe the X-ray crystal structure of EthR, a homodimer with an entirely helical structure showing similarities to TetR family members. Each monomer contained a fortuitous ligand identified as hexadecyl octanoate. The crystal structure of EthR purified in M. smegmatis revealed the presence of a comparable ligand. The binding of hexadecyl octanoate to EthR induces a conformational state incompatible with repressor function, which should lead to ethA derepression and consequently to an increased sensitivity to ethionamide and other thioamides. A related, more hydrophilic ketone was found to exhibit synergistic antimycobacterial effects when tested together with ethionamide, indicating that this strategy may help reduce the dosage of potent antibacterial compounds that otherwise are too toxic to be used as first-line drugs.

Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis.,Frenois F, Engohang-Ndong J, Locht C, Baulard AR, Villeret V Mol Cell. 2004 Oct 22;16(2):301-7. PMID:15494316^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, Locht C, Besra GS. Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem. 2000 Sep 8;275(36):28326-31. PMID:10869356 doi:10.1074/jbc.M003744200
↑ DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-82. PMID:10944230
↑ Frenois F, Engohang-Ndong J, Locht C, Baulard AR, Villeret V. Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis. Mol Cell. 2004 Oct 22;16(2):301-7. PMID:15494316 doi:10.1016/j.molcel.2004.09.020

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u9n"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the transcriptional regulator EthR in a ligand bound conformation opens therapeutic perspectives against tuberculosis and leprosy==
 <StructureSection load='1u9n' size='340' side='right' caption='[[1u9n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u9o|1u9o]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u9n OCA], [http://pdbe.org/1u9n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u9n RCSB], [http://www.ebi.ac.uk/pdbsum/1u9n PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u9n OCA], [http://pdbe.org/1u9n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u9n RCSB], [http://www.ebi.ac.uk/pdbsum/1u9n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u9n ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u9/1u9n_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u9/1u9n_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1u9n

From Proteopedia

Revision as of 08:37, 21 March 2018

Crystal structure of the transcriptional regulator EthR in a ligand bound conformation opens therapeutic perspectives against tuberculosis and leprosy

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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