View source for 6fe1


==Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.==
<StructureSection load='6fe1' size='340' side='right'caption='[[6fe1]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fe1]] 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=6FE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FE1 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V14:3-(CYCLOOCTYLAMINO)-2,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V14</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=6fe1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fe1 OCA], [https://pdbe.org/6fe1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fe1 RCSB], [https://www.ebi.ac.uk/pdbsum/6fe1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fe1 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human carbonic anhydrase (CA) IX has emerged as a promising anticancer target and a diagnostic biomarker for solid hypoxic tumors. Novel fluorinated CA IX inhibitors exhibited up to 50 pM affinity towards the recombinant human CA IX, selectivity over other CAs, and direct binding to Zn(II) in the active site of CA IX inducing novel conformational changes as determined by X-ray crystallography. Mass spectrometric gas-analysis confirmed the CA IX-based mechanism of the inhibitors in a CRISPR/Cas9-mediated CA IX knockout in HeLa cells. Hypoxia-induced extracellular acidification was significantly reduced in HeLa, H460, MDA-MB-231, and A549 cells exposed to the compounds, with the IC50 values up to 1.29 nM. A decreased clonogenic survival was observed when hypoxic H460 3D spheroids were incubated with our lead compound. These novel compounds are therefore promising agents for CA IX-specific therapy.

Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells.,Kazokaite J, Niemans R, Dudutiene V, Becker HM, Leitans J, Zubriene A, Baranauskiene L, Gondi G, Zeidler R, Matuliene J, Tars K, Yaromina A, Lambin P, Dubois LJ, Matulis D Oncotarget. 2018 Jun 1;9(42):26800-26816. doi: 10.18632/oncotarget.25508., eCollection 2018 Jun 1. PMID:29928486<ref>PMID:29928486</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fe1" 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]]