5dvx: Difference between revisions
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==Crystal structure of the catalytic-domain of human carbonic anhydrase IX at 1.6 angstrom resolution== | |||
<StructureSection load='5dvx' size='340' side='right' caption='[[5dvx]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dvx]] is a 2 chain structure. 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> | |||
</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> | |||
<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'>[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> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:27439028</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Driscoll, J | <div class="pdbe-citations 5dvx" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Carbonate dehydratase]] | |||
[[Category: Driscoll, J M]] | |||
[[Category: Mahon, B P]] | |||
[[Category: McKenna, R]] | |||
[[Category: Socorro, L]] | [[Category: Socorro, L]] | ||
[[Category: | [[Category: Carbonic anhydrase ix]] | ||
[[Category: Catalytic domain]] | |||
[[Category: Lyase]] | |||
[[Category: Water network]] |