4m3g

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:23, 1 March 2024) (edit) (undo)
 
(4 intermediate revisions 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='4m3g' size='340' side='right' caption='[[4m3g]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+
<StructureSection load='4m3g' size='340' side='right'caption='[[4m3g]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4m3g]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M3G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M3G FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4m3g]] 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=4M3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M3G FirstGlance]. <br>
-
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2G1:4-(2-METHYL-1,3-THIAZOL-4-YL)-N-(3,3,3-TRIFLUOROPROPYL)BENZENESULFONAMIDE'>2G1</scene><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><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m3b|4m3b]], [[4m3d|4m3d]], [[4m3e|4m3e]], [[4m3f|4m3f]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2G1:4-(2-METHYL-1,3-THIAZOL-4-YL)-N-(3,3,3-TRIFLUOROPROPYL)BENZENESULFONAMIDE'>2G1</scene></td></tr>
-
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m3g RCSB], [http://www.ebi.ac.uk/pdbsum/4m3g PDBsum]</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=4m3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m3g OCA], [https://pdbe.org/4m3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m3g RCSB], [https://www.ebi.ac.uk/pdbsum/4m3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m3g ProSAT]</span></td></tr>
-
<table>
+
</table>
-
<div style="background-color:#fffaf0;">
+
== Function ==
-
== Publication Abstract from PubMed ==
+
[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>
-
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>
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
==See Also==
-
</div>
+
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
== 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]]
+

Current revision

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

PDB ID 4m3g

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m3g"
Personal tools