6fe0: Difference between revisions
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==Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.== | |||
<StructureSection load='6fe0' size='340' side='right'caption='[[6fe0]], [[Resolution|resolution]] 1.91Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fe0]] 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=6FE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FE0 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]] 1.91Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V90:2-(CYCLOOCTYLAMINO)-3,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFANYL]BENZENESULFONAMIDE'>V90</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=6fe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fe0 OCA], [https://pdbe.org/6fe0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fe0 RCSB], [https://www.ebi.ac.uk/pdbsum/6fe0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fe0 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 == | |||
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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Leitans | <div class="pdbe-citations 6fe0" style="background-color:#fffaf0;"></div> | ||
[[Category: Tars | |||
==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]] | |||
Latest revision as of 15:38, 6 November 2024
Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide.
Structural highlights
FunctionCAH9_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.[1] Publication Abstract from PubMedHuman 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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