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| | <StructureSection load='5dvx' size='340' side='right'caption='[[5dvx]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='5dvx' size='340' side='right'caption='[[5dvx]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dvx]] is a 2 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=5DVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DVX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dvx]] is a 2 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=5DVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DVX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.598Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA9, G250, MN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5dvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvx OCA], [https://pdbe.org/5dvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dvx RCSB], [https://www.ebi.ac.uk/pdbsum/5dvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvx ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvx OCA], [http://pdbe.org/5dvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dvx RCSB], [http://www.ebi.ac.uk/pdbsum/5dvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvx 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: Driscoll, J M]] | + | [[Category: Driscoll JM]] |
| - | [[Category: Mahon, B P]] | + | [[Category: Mahon BP]] |
| - | [[Category: McKenna, R]] | + | [[Category: McKenna R]] |
| - | [[Category: Socorro, L]] | + | [[Category: Socorro L]] |
| - | [[Category: Carbonic anhydrase ix]]
| + | |
| - | [[Category: Catalytic domain]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Water network]]
| + | |
| 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 (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anti-cancer agents with some entering Phase I clinical trials. hCA IX is a transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical/biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible and its catalytic efficiency is suggested to be correlated directly with its stability between 3.0<pH<8.0 but not at pH>8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 A resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low pH tumor microenvironments, and may be applicable to determining pH-related effects on other enzymes.
Structure of carbonic anhydrase IX is adapted for low pH catalysis.,Mahon BP, Bhatt A, Socorro L, Driscoll JM, Okoh C, Lomelino CL, Mboge MY, Kurian JJ, Tu C, Agbandje-McKenna M, Frost SC, McKenna R Biochemistry. 2016 Jul 20. PMID:27439028[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
- ↑ Mahon BP, Bhatt A, Socorro L, Driscoll JM, Okoh C, Lomelino CL, Mboge MY, Kurian JJ, Tu C, Agbandje-McKenna M, Frost SC, McKenna R. Structure of carbonic anhydrase IX is adapted for low pH catalysis. Biochemistry. 2016 Jul 20. PMID:27439028 doi:http://dx.doi.org/10.1021/acs.biochem.6b00243
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