4xyc: Difference between revisions
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==NANOMOLAR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE 1: SYNTHESIS, BIOLOGICAL EVALUATION AND X-RAY CRYSTALLOGRAPHIC STUDIES== | |||
<StructureSection load='4xyc' size='340' side='right'caption='[[4xyc]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4xyc]] is a 24 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=4XYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XYC FirstGlance]. <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]] 3.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2K9:9-PHENYL-4H-IMIDAZO[1,2-A]INDENO[1,2-E]PYRAZIN-4-ONE'>2K9</scene></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=4xyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xyc OCA], [https://pdbe.org/4xyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xyc RCSB], [https://www.ebi.ac.uk/pdbsum/4xyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xyc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GLN1B_MYCTO GLN1B_MYCTO] Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion. Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis.[UniProtKB:P9WN39] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit M. tuberculosis glutamine synthetase (GlnA1) has been identified by high throughput screening. Exploration of this series was performed owing to a short chemistry program. Despite possibly nanomolar inhibitions, none of these compounds was active on whole cell Mtb, suggesting that GlnA1 may not be a suitable target to find new anti-tubercular drugs. | |||
Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1: Synthesis, biological evaluation and X-ray crystallographic studies.,Couturier C, Silve S, Morales R, Pessegue B, Llopart S, Nair A, Bauer A, Scheiper B, Poverlein C, Ganzhorn A, Lagrange S, Bacque E Bioorg Med Chem Lett. 2015 Apr 1;25(7):1455-9. doi: 10.1016/j.bmcl.2015.02.035., Epub 2015 Feb 23. PMID:25770781<ref>PMID:25770781</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4xyc" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Glutamine synthetase 3D structures|Glutamine synthetase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Scheiper | [[Category: Bacque E]] | ||
[[Category: | [[Category: Bauer A]] | ||
[[Category: Couturier C]] | |||
[[Category: Ganzhorn A]] | |||
[[Category: Lagrange S]] | |||
[[Category: Llopart S]] | |||
[[Category: Morales R]] | |||
[[Category: Nair A]] | |||
[[Category: Ppessegue B]] | |||
[[Category: Scheiper B]] | |||
[[Category: Silve S]] | |||
[[Category: Poeverlein c]] | |||
Latest revision as of 13:51, 10 January 2024
NANOMOLAR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE 1: SYNTHESIS, BIOLOGICAL EVALUATION AND X-RAY CRYSTALLOGRAPHIC STUDIESNANOMOLAR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE 1: SYNTHESIS, BIOLOGICAL EVALUATION AND X-RAY CRYSTALLOGRAPHIC STUDIES
Structural highlights
FunctionGLN1B_MYCTO Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion. Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis.[UniProtKB:P9WN39] Publication Abstract from PubMedA series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit M. tuberculosis glutamine synthetase (GlnA1) has been identified by high throughput screening. Exploration of this series was performed owing to a short chemistry program. Despite possibly nanomolar inhibitions, none of these compounds was active on whole cell Mtb, suggesting that GlnA1 may not be a suitable target to find new anti-tubercular drugs. Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1: Synthesis, biological evaluation and X-ray crystallographic studies.,Couturier C, Silve S, Morales R, Pessegue B, Llopart S, Nair A, Bauer A, Scheiper B, Poverlein C, Ganzhorn A, Lagrange S, Bacque E Bioorg Med Chem Lett. 2015 Apr 1;25(7):1455-9. doi: 10.1016/j.bmcl.2015.02.035., Epub 2015 Feb 23. PMID:25770781[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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