9r0l
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Three dimensional structure of human carbonic anhydrase XII in complex with sulfonamide== | |
| + | <StructureSection load='9r0l' size='340' side='right'caption='[[9r0l]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9r0l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9R0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9R0L 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]] 1.45Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H9A:3-(cyclooctylamino)-2,6-bis(fluoranyl)-4-(3-oxidanylpropylsulfonyl)-5-piperidin-1-yl-benzenesulfonamide'>A1H9A</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=9r0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9r0l OCA], [https://pdbe.org/9r0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9r0l RCSB], [https://www.ebi.ac.uk/pdbsum/9r0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9r0l ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN] Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:[https://omim.org/entry/143860 143860]. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.<ref>PMID:21035102</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN] Reversible hydration of carbon dioxide. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The development of selective drug candidate molecules for cancer-related carbonic anhydrase isozymes IX and XII is challenging due to high homology binding sites among 12 catalytically active isozymes. Starting from the trifluorinated benzenesulfonamide with cyclooctylamino substituent at the meta position, we designed and synthesized di-meta-substituted fluorinated benzenesulfonamides with up to 10-fold affinity improvement for CAIX, resulting in low picomolar binders. The resulting CAIX-targeting compounds showed up to 1000-fold selectivity over off-target CA isozymes. The crystal structures of CAIX and CAXII complexes with synthesized compounds revealed detailed insights into protein-ligand interactions and adopted complex conformation. The potential of compounds with reduced off-target effects as possible anticancer drugs is supported by this study. | ||
| - | + | Di-meta-Substituted Fluorinated Benzenesulfonamides as Potent and Selective Anticancer Inhibitors of Carbonic Anhydrase IX and XII.,Vaskevicius A, Zvirblis M, Kurtenoka M, Leitans J, Manakova E, Paketuryte-Latve V, Kvietkauskaite A, Kazaks A, Eimonta V, Cerepenkaite K, Kazokaite-Adomaitiene J, MickeviciuÌ
te A, Juozapaitiene V, Tars K, Grazulis S, Matuliene J, Dudutiene V, Shubin K, Matulis D, Zubriene A J Med Chem. 2025 Sep 11;68(17):18389-18406. doi: 10.1021/acs.jmedchem.5c01142. , Epub 2025 Aug 20. PMID:40833423<ref>PMID:40833423</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Eimonta | + | <div class="pdbe-citations 9r0l" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Eimonta V]] | ||
| + | [[Category: Leitans J]] | ||
| + | [[Category: Tars K]] | ||
Current revision
Three dimensional structure of human carbonic anhydrase XII in complex with sulfonamide
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