8dr2: Difference between revisions
New page: '''Unreleased structure''' The entry 8dr2 is ON HOLD Authors: Marapaka, A.K., Das, C., Flaherty, D.P., Yadav, R. Description: Crystal structure of Neisseria gonorrhoeae carbonic anhydr... |
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==Crystal structure of Neisseria gonorrhoeae carbonic anhydrase with 2-cyclohexyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide== | |||
<StructureSection load='8dr2' size='340' side='right'caption='[[8dr2]], [[Resolution|resolution]] 2.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8dr2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_gonorrhoeae Neisseria gonorrhoeae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DR2 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]] 2.81Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TE3:2-cyclohexyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide'>TE3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8dr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dr2 OCA], [https://pdbe.org/8dr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dr2 RCSB], [https://www.ebi.ac.uk/pdbsum/8dr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dr2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH_NEIGO CAH_NEIGO] Reversible hydration of carbon dioxide. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Drug-resistant Neisseria gonorrhoeae is a critical threat to public health, and bacterial carbonic anhydrases expressed by N. gonorrhoeae are potential new therapeutic targets to combat this pathogen. To further expand upon our recent reports of bacterial carbonic anhydrase inhibitors for the treatment of N. gonorrhoeae, our team has solved ligand-bound crystal structures of the FDA-approved carbonic anhydrase inhibitor acetazolamide, along with three analogs, in complex with the essential alpha-carbonic anhydrase isoform from N. gonorrhoeae. The structural data for the analogs presented bound to N. gonorrhoeae alpha-carbonic anhydrase supports the observed structure-activity relationship for in vitro inhibition with this scaffold against the enzyme. Moreover, the ligand-bound structures indicate differences in binding poses compared to those traditionally observed with the close human ortholog carbonic anhydrase II. These results present key differences in inhibitor binding between N. gonorrhoeae alpha-carbonic anhydrase and the human carbonic anhydrase II isoform. | |||
Structural Characterization of Thiadiazolesulfonamide Inhibitors Bound to Neisseria gonorrhoeae alpha-Carbonic Anhydrase.,Marapaka AK, Nocentini A, Youse MS, An W, Holly KJ, Das C, Yadav R, Seleem MN, Supuran CT, Flaherty DP ACS Med Chem Lett. 2022 Dec 6;14(1):103-109. doi: 10.1021/acsmedchemlett.2c00471. , eCollection 2023 Jan 12. PMID:36655133<ref>PMID:36655133</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8dr2" style="background-color:#fffaf0;"></div> | ||
[[Category: Das | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Neisseria gonorrhoeae]] | |||
[[Category: Das C]] | |||
[[Category: Flaherty DP]] | |||
[[Category: Marapaka AK]] | |||
[[Category: Yadav R]] | |||
Latest revision as of 12:49, 9 October 2024
Crystal structure of Neisseria gonorrhoeae carbonic anhydrase with 2-cyclohexyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamideCrystal structure of Neisseria gonorrhoeae carbonic anhydrase with 2-cyclohexyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
Structural highlights
FunctionCAH_NEIGO Reversible hydration of carbon dioxide. Publication Abstract from PubMedDrug-resistant Neisseria gonorrhoeae is a critical threat to public health, and bacterial carbonic anhydrases expressed by N. gonorrhoeae are potential new therapeutic targets to combat this pathogen. To further expand upon our recent reports of bacterial carbonic anhydrase inhibitors for the treatment of N. gonorrhoeae, our team has solved ligand-bound crystal structures of the FDA-approved carbonic anhydrase inhibitor acetazolamide, along with three analogs, in complex with the essential alpha-carbonic anhydrase isoform from N. gonorrhoeae. The structural data for the analogs presented bound to N. gonorrhoeae alpha-carbonic anhydrase supports the observed structure-activity relationship for in vitro inhibition with this scaffold against the enzyme. Moreover, the ligand-bound structures indicate differences in binding poses compared to those traditionally observed with the close human ortholog carbonic anhydrase II. These results present key differences in inhibitor binding between N. gonorrhoeae alpha-carbonic anhydrase and the human carbonic anhydrase II isoform. Structural Characterization of Thiadiazolesulfonamide Inhibitors Bound to Neisseria gonorrhoeae alpha-Carbonic Anhydrase.,Marapaka AK, Nocentini A, Youse MS, An W, Holly KJ, Das C, Yadav R, Seleem MN, Supuran CT, Flaherty DP ACS Med Chem Lett. 2022 Dec 6;14(1):103-109. doi: 10.1021/acsmedchemlett.2c00471. , eCollection 2023 Jan 12. PMID:36655133[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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