View source for 6qn6


==Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide==
<StructureSection load='6qn6' size='340' side='right'caption='[[6qn6]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qn6]] 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=6QN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QN6 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]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J8Q:~{N}-butyl-4-chloranyl-2-(2-phenylethylsulfanyl)-5-sulfamoyl-benzamide'>J8Q</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=6qn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qn6 OCA], [https://pdbe.org/6qn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qn6 RCSB], [https://www.ebi.ac.uk/pdbsum/6qn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qn6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
By applying an approach of a "ring with two tails", a series of novel inhibitors possessing high-affinity and significant selectivity towards selected carbonic anhydrase (CA) isoforms has been designed. The "ring" consists of 2-chloro/bromo-benzenesulfonamide, where the sulfonamide group is as an anchor coordinating the Zn(II) in the active site of CAs, and halogen atom orients the ring affecting the affinity and selectivity. First "tail" is a substituent containing carbonyl, carboxyl, hydroxyl, ether groups or hydrophilic amide linkage. The second "tail" contains aryl- or alkyl-substituents attached through a sulfanyl or sulfonyl group. Both "tails" are connected to the benzene ring and play a crucial role in selectivity. Varying the substituents, we designed compounds selective for CA VII, CA IX, CA XII, or CA XIV. Since due to binding-linked protonation reactions the binding-ready fractions of the compound and protein are much lower than one, the "intrinsic" affinities were calculated that should be used to study correlations between crystal structures and the thermodynamics of binding for rational drug design. The "intrinsic" affinities together with the intrinsic enthalpies and entropies of binding together with co-crystal structures were used demonstrate structural factors determining major contributions for compound affinity and selectivity.

Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms.,Zaksauskas A, Capkauskaite E, Jezepcikas L, Linkuviene V, Paketuryte V, Smirnov A, Leitans J, Kazaks A, Dvinskis E, Manakova E, Grazulis S, Tars K, Matulis D Eur J Med Chem. 2020 Jan 1;185:111825. doi: 10.1016/j.ejmech.2019.111825. Epub, 2019 Oct 31. PMID:31740053<ref>PMID:31740053</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qn6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Leitans J]]
[[Category: Tars K]]