4tzk: Difference between revisions

Revision as of 07:53, 22 March 2023

Crystal structure of Mycobacterium tuberculosis enoyl reductase (INHA) complexed WITH 1-CYCLOHEXYL-N-(3,5-DICHLOROPHENYL)-5-OXOPYRROLIDINE-3-CARBOXAMIDE

Structural highlights

4tzk is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. This structure supersedes the now removed PDB entry 2h7m. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	641, NAD
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

INHA_MYCTU

Publication Abstract from PubMed

In view of the worldwide spread of multidrug resistance of Mycobacterium tuberculosis, there is an urgent need to discover antituberculosis agent with novel structures. InhA, the enoyl acyl carrier protein reductase (ENR) from M. tuberculosis, is one of the key enzymes involved in the mycobacterial fatty acid elongation cycle and has been validated as an effective antimicrobial target. We report here the discovery, through high-throughput screening, of a series of pyrrolidine carboxamides as a novel class of potent InhA inhibitors. Crystal structures of InhA complexed with three inhibitors have been used to elucidate the inhibitor binding mode. The potency of the lead compound was improved over 160-fold by subsequent optimization through iterative microtiter library synthesis followed by in situ activity screening without purification. Resolution of racemic mixtures of several inhibitors indicate that only one enantiomer is active as an inhibitor of InhA.

Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis.,He X, Alian A, Stroud R, Ortiz de Montellano PR J Med Chem. 2006 Oct 19;49(21):6308-23. PMID:17034137^[1]

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

References

↑ He X, Alian A, Stroud R, Ortiz de Montellano PR. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis. J Med Chem. 2006 Oct 19;49(21):6308-23. PMID:17034137 doi:https://dx.doi.org/10.1021/jm060715y

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OCA

[1] He X, Alian A, Stroud R, Ortiz de Montellano PR. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis. J Med Chem. 2006 Oct 19;49(21):6308-23. PMID:17034137 doi:https://dx.doi.org/10.1021/jm060715y

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='4tzk' size='340' side='right'caption='[[4tzk]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4tzk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2h7m 2h7m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TZK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TZK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4tzk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2h7m 2h7m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TZK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=641:(3S)-1-CYCLOHEXYL-N-(3,5-DICHLOROPHENYL)-5-OXOPYRROLIDINE-3-CARBOXAMIDE'>641</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=641:(3S)-1-CYCLOHEXYL-N-(3,5-DICHLOROPHENYL)-5-OXOPYRROLIDINE-3-CARBOXAMIDE'>641</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4trj|4trj]], [[4tzt|4tzt]], [[4u0j|4u0j]], [[4u0k|4u0k]]</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=4tzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tzk OCA], [https://pdbe.org/4tzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tzk RCSB], [https://www.ebi.ac.uk/pdbsum/4tzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tzk ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inhA, Rv1484, MTCY277.05 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tzk OCA], [http://pdbe.org/4tzk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tzk RCSB], [http://www.ebi.ac.uk/pdbsum/4tzk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tzk 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 27: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Alian, A]]
+[[Category: Alian A]]
-[[Category: He, X]]
+[[Category: He X]]
-[[Category: Montellano, P R.Ortiz de]]
+[[Category: Ortiz de Montellano PR]]
-[[Category: Stroud, R M]]
+[[Category: Stroud RM]]
-[[Category: Oxidoreductase]]
-[[Category: Pyrrolidine carboxamide]]

4tzk: Difference between revisions

Revision as of 07:53, 22 March 2023

Crystal structure of Mycobacterium tuberculosis enoyl reductase (INHA) complexed WITH 1-CYCLOHEXYL-N-(3,5-DICHLOROPHENYL)-5-OXOPYRROLIDINE-3-CARBOXAMIDE

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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