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4cod

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Revision as of 07:24, 14 September 2022

Encoded library technology as a source of hits for the discovery and lead optimization of a potent and selective class of bactericidal direct inhibitors of Mycobacterium tuberculosis InhA

Structural highlights

4cod is a 4 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[INHA_MYCTU]

Publication Abstract from PubMed

Tuberculosis (TB) is one of the world's oldest and deadliest diseases, killing a person every 20 s. InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis, is the target of the frontline antitubercular drug isoniazid (INH). Compounds that directly target InhA and do not require activation by mycobacterial catalase peroxidase KatG are promising candidates for treating infections caused by INH resistant strains. The application of the encoded library technology (ELT) to the discovery of direct InhA inhibitors yielded compound 7 endowed with good enzymatic potency but with low antitubercular potency. This work reports the hit identification, the selected strategy for potency optimization, the structure-activity relationships of a hundred analogues synthesized, and the results of the in vivo efficacy studies performed with the lead compound 65.

Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium tuberculosis InhA.,Encinas L, O'Keefe H, Neu M, Remuinan MJ, Patel AM, Guardia A, Davie CP, Perez-Macias N, Yang H, Convery MA, Messer JA, Perez-Herran E, Centrella PA, Alvarez-Gomez D, Clark MA, Huss S, O'Donovan GK, Ortega-Muro F, McDowell W, Castaneda P, Arico-Muendel CC, Pajk S, Rullas J, Angulo-Barturen I, Alvarez-Ruiz E, Mendoza-Losana A, Ballell Pages L, Castro-Pichel J, Evindar G J Med Chem. 2014 Feb 5. PMID:24450589^[1]

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

References

↑ Encinas L, O'Keefe H, Neu M, Remuinan MJ, Patel AM, Guardia A, Davie CP, Perez-Macias N, Yang H, Convery MA, Messer JA, Perez-Herran E, Centrella PA, Alvarez-Gomez D, Clark MA, Huss S, O'Donovan GK, Ortega-Muro F, McDowell W, Castaneda P, Arico-Muendel CC, Pajk S, Rullas J, Angulo-Barturen I, Alvarez-Ruiz E, Mendoza-Losana A, Ballell Pages L, Castro-Pichel J, Evindar G. Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium tuberculosis InhA. J Med Chem. 2014 Feb 5. PMID:24450589 doi:http://dx.doi.org/10.1021/jm401326j

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cod"

@@ Line 3: / Line 3: @@
 <StructureSection load='4cod' size='340' side='right'caption='[[4cod]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cod]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4COD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cod]] 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=4COD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4COD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KV1:N-((3R,5S)-1-(BENZOFURAN-3-CARBONYL)-5-(ETHYLCARBAMOYL)PYRROLIDIN-3-YL)-3-ETHYL-1-METHYL-1H-PYRAZOLE-5-CARBOXAMIDE'>KV1</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KV1:N-((3R,5S)-1-(BENZOFURAN-3-CARBONYL)-5-(ETHYLCARBAMOYL)PYRROLIDIN-3-YL)-3-ETHYL-1-METHYL-1H-PYRAZOLE-5-CARBOXAMIDE'>KV1</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=4cod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cod OCA], [https://pdbe.org/4cod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cod RCSB], [https://www.ebi.ac.uk/pdbsum/4cod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cod ProSAT]</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=4cod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cod OCA], [http://pdbe.org/4cod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cod RCSB], [http://www.ebi.ac.uk/pdbsum/4cod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cod ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Castro-Pichel, J]]
+[[Category: Mycobacterium tuberculosis]]
-[[Category: Convery, M A]]
+[[Category: Castro-Pichel J]]
-[[Category: Encinas, L]]
+[[Category: Convery MA]]
-[[Category: Evindar, G]]
+[[Category: Encinas L]]
-[[Category: McDowell, W]]
+[[Category: Evindar G]]
-[[Category: Mendoza-Losana, A]]
+[[Category: McDowell W]]
-[[Category: Neu, M]]
+[[Category: Mendoza-Losana A]]
-[[Category: OKeefe, H]]
+[[Category: Neu M]]
-[[Category: Pages, L B]]
+[[Category: OKeefe H]]
-[[Category: Elt]]
+[[Category: Pages LB]]
-[[Category: Encoded library technology]]
-[[Category: Isoniazid]]
-[[Category: L-proline]]
-[[Category: Transferase]]

4cod

From Proteopedia

Revision as of 07:24, 14 September 2022

Encoded library technology as a source of hits for the discovery and lead optimization of a potent and selective class of bactericidal direct inhibitors of Mycobacterium tuberculosis InhA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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