4m3f: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:


==Rapid and efficient design of new inhibitors of Mycobacterium tuberculosis transcriptional repressor EthR using fragment growing, merging and linking approaches==
==Rapid and efficient design of new inhibitors of Mycobacterium tuberculosis transcriptional repressor EthR using fragment growing, merging and linking approaches==
<StructureSection load='4m3f' size='340' side='right' caption='[[4m3f]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='4m3f' size='340' side='right'caption='[[4m3f]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4m3f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M3F FirstGlance]. <br>
<table><tr><td colspan='2'>[[4m3f]] is a 1 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=4M3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M3F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2D1:N-(3-METHYLBUTYL)-4-(2-METHYL-1,3-THIAZOL-4-YL)BENZENESULFONAMIDE'>2D1</scene></td></tr>
</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&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m3b|4m3b]], [[4m3d|4m3d]], [[4m3e|4m3e]], [[4m3g|4m3g]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2D1:N-(3-METHYLBUTYL)-4-(2-METHYL-1,3-THIAZOL-4-YL)BENZENESULFONAMIDE'>2D1</scene></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=4m3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3f OCA], [http://pdbe.org/4m3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m3f RCSB], [http://www.ebi.ac.uk/pdbsum/4m3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m3f ProSAT]</span></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=4m3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3f OCA], [https://pdbe.org/4m3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m3f RCSB], [https://www.ebi.ac.uk/pdbsum/4m3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m3f ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ETHR_MYCTU ETHR_MYCTU]] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).<ref>PMID:10869356</ref> <ref>PMID:10944230</ref>
[https://www.uniprot.org/uniprot/ETHR_MYCTU ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).<ref>PMID:10869356</ref> <ref>PMID:10944230</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tuberculosis remains a major cause of mortality and morbidity, killing each year more than one million people. Although the combined use of first line antibiotics (isoniazid, rifampicin, pyrazinamide, and ethambutol) is efficient to treat most patients, the rapid emergence of multidrug resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. Mycobacterial transcriptional repressor EthR is a key player in the control of second-line drugs bioactivation such as ethionamide and has been shown to impair the sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. As a way to identify new potent ligands of this protein, we have developed fragment-based approaches. In the current study, we combined surface plasmon resonance assay, X-ray crystallography, and ligand efficiency driven design for the rapid discovery and optimization of new chemotypes of EthR ligands starting from a fragment. The design, synthesis, and in vitro and ex vivo activities of these compounds will be discussed.


Ligand Efficiency Driven Design of New Inhibitors of Mycobacterium tuberculosis Transcriptional Repressor EthR Using Fragment Growing, Merging, and Linking Approaches.,Villemagne B, Flipo M, Blondiaux N, Crauste C, Malaquin S, Leroux F, Piveteau C, Villeret V, Brodin P, Villoutreix BO, Sperandio O, Soror SH, Wohlkonig A, Wintjens R, Deprez B, Baulard AR, Willand N J Med Chem. 2014 Jun 12;57(11):4876-88. doi: 10.1021/jm500422b. Epub 2014 May 28. PMID:24818704<ref>PMID:24818704</ref>
==See Also==
 
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4m3f" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Baulard, A]]
[[Category: Large Structures]]
[[Category: Blondiaux, N]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Brodin, P]]
[[Category: Baulard A]]
[[Category: Crauste, C]]
[[Category: Blondiaux N]]
[[Category: Deprez, B]]
[[Category: Brodin P]]
[[Category: Flipo, M]]
[[Category: Crauste C]]
[[Category: Leroux, F]]
[[Category: Deprez B]]
[[Category: Malaquin, S]]
[[Category: Flipo M]]
[[Category: Piveteau, C]]
[[Category: Leroux F]]
[[Category: Sperandio, O]]
[[Category: Malaquin S]]
[[Category: Villemagne, B]]
[[Category: Piveteau C]]
[[Category: Villeret, V]]
[[Category: Sperandio O]]
[[Category: Villoutreix, B]]
[[Category: Villemagne B]]
[[Category: Willand, N]]
[[Category: Villeret V]]
[[Category: Wintjens, R]]
[[Category: Villoutreix B]]
[[Category: Wohlkonig, A]]
[[Category: Willand N]]
[[Category: Helix-turn-helix dna binding protein]]
[[Category: Wintjens R]]
[[Category: Inhibitor]]
[[Category: Wohlkonig A]]
[[Category: Tetr-family]]
[[Category: Transcription repressor-inhibitor complex]]
[[Category: Transcriptional regulatory repressor]]

Latest revision as of 12:23, 1 March 2024

Rapid and efficient design of new inhibitors of Mycobacterium tuberculosis transcriptional repressor EthR using fragment growing, merging and linking approaches

4m3f, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=4m3f&oldid=4075198"