5fl6: Difference between revisions
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==Three dimensional structure of human carbonic anhydrase IX in complex with 5-(1-(4-Methylphenyl)-1H-1,2,3-triazol-4-yl)thiophene-2- sulfonamide== | ==Three dimensional structure of human carbonic anhydrase IX in complex with 5-(1-(4-Methylphenyl)-1H-1,2,3-triazol-4-yl)thiophene-2- sulfonamide== | ||
<StructureSection load='5fl6' size='340' side='right' caption='[[5fl6]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='5fl6' size='340' side='right'caption='[[5fl6]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fl6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FL6 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5fl6]] 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=5FL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FL6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=Y0R:5-[1-(4-METHYLPHENYL)-1,2,3-TRIAZOL-4-YL]THIOPHENE-2-SULFONAMIDE'>Y0R</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=Y0R:5-[1-(4-METHYLPHENYL)-1,2,3-TRIAZOL-4-YL]THIOPHENE-2-SULFONAMIDE'>Y0R</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=5fl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fl6 OCA], [https://pdbe.org/5fl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fl6 RCSB], [https://www.ebi.ac.uk/pdbsum/5fl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fl6 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5fl6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5fl6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Leitans J]] | ||
[[Category: | [[Category: Tars K]] | ||
[[Category: | [[Category: Zalubovskis R]] | ||
Latest revision as of 09:55, 19 July 2023
Three dimensional structure of human carbonic anhydrase IX in complex with 5-(1-(4-Methylphenyl)-1H-1,2,3-triazol-4-yl)thiophene-2- sulfonamideThree dimensional structure of human carbonic anhydrase IX in complex with 5-(1-(4-Methylphenyl)-1H-1,2,3-triazol-4-yl)thiophene-2- sulfonamide
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 IX (CA IX) is overexpressed in a number of solid tumors and is considered to be a marker for cellular hypoxia that it is not produced in most normal tissues. CA IX contributes to the acidification of the extracellular matrix, which, in turn, favors tumor growth and metastasis. Therefore, CA IX is considered to be a promising anti-cancer drug target. However, the ability to specifically target CA IX is challenging due to the fact that the human genome encodes 15 different carbonic anhydrase isoforms that have a high degree of homology. Furthermore, structure-based drug design of CA IX inhibitors so far has been largely unsuccessful due to technical difficulties regarding the expression and crystallization of the enzyme. Currently, only one baculovirus-produced CA IX structure in complex with a nonspecific CA inhibitor, acetazolamide, is available in Protein Data Bank. We have developed an efficient system for the production of the catalytic domain of CA IX in methylotrophic yeast Pichia pastoris. The produced protein can be easily crystallized in the presence of inhibitors, as we have demonstrated for several 2-thiophene-sulfonamide compounds. We have also observed significant differences in the binding mode of chemically identical compounds to CA IX and CA II, which can be further exploited in the design of CA IX-specific inhibitors. Efficient Expression and Crystallization System of Cancer-Associated Carbonic Anhydrase Isoform IX.,Leitans J, Kazaks A, Balode A, Ivanova J, Zalubovskis R, Supuran CT, Tars K J Med Chem. 2015 Nov 25;58(22):9004-9. doi: 10.1021/acs.jmedchem.5b01343. Epub, 2015 Nov 10. PMID:26522624[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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