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| | <StructureSection load='5fl4' size='340' side='right'caption='[[5fl4]], [[Resolution|resolution]] 1.82Å' scene=''> | | <StructureSection load='5fl4' size='340' side='right'caption='[[5fl4]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fl4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FL4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FL4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fl4]] 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=5FL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FL4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9FK:5-(1-NAPHTHALEN-1-YL-1,2,3-TRIAZOL-4-YL)THIOPHENE-2-SULFONAMIDE'>9FK</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fl5|5fl5]], [[5fl6|5fl6]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9FK:5-(1-NAPHTHALEN-1-YL-1,2,3-TRIAZOL-4-YL)THIOPHENE-2-SULFONAMIDE'>9FK</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></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=5fl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fl4 OCA], [https://pdbe.org/5fl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fl4 RCSB], [https://www.ebi.ac.uk/pdbsum/5fl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fl4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fl4 OCA], [http://pdbe.org/5fl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fl4 RCSB], [http://www.ebi.ac.uk/pdbsum/5fl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fl4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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 == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carbonate dehydratase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leitans, J]] | + | [[Category: Leitans J]] |
| - | [[Category: Tars, K]] | + | [[Category: Tars K]] |
| - | [[Category: Zalubovskis, R]] | + | [[Category: Zalubovskis R]] |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
Human 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 Also
References
- ↑ Hilvo M, Baranauskiene L, Salzano AM, Scaloni A, Matulis D, Innocenti A, Scozzafava A, Monti SM, Di Fiore A, De Simone G, Lindfors M, Janis J, Valjakka J, Pastorekova S, Pastorek J, Kulomaa MS, Nordlund HR, Supuran CT, Parkkila S. Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. J Biol Chem. 2008 Oct 10;283(41):27799-809. doi: 10.1074/jbc.M800938200. Epub, 2008 Aug 13. PMID:18703501 doi:http://dx.doi.org/10.1074/jbc.M800938200
- ↑ Leitans J, Kazaks A, Balode A, Ivanova J, Zalubovskis R, Supuran CT, Tars K. Efficient Expression and Crystallization System of Cancer-Associated Carbonic Anhydrase Isoform IX. J Med Chem. 2015 Nov 25;58(22):9004-9. doi: 10.1021/acs.jmedchem.5b01343. Epub, 2015 Nov 10. PMID:26522624 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01343
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