4ht2
From Proteopedia
(Difference between revisions)
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| - | {{STRUCTURE_4ht2| PDB=4ht2 | SCENE= }} | ||
| - | ===Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.=== | ||
| - | {{ABSTRACT_PUBMED_23394791}} | ||
| - | ==Disease== | + | ==Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.== |
| + | <StructureSection load='4ht2' size='340' side='right' caption='[[4ht2]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ht2]] 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=4HT2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HT2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=V50:4-[(4,6-DIMETHYLPYRIMIDIN-2-YL)THIO]-2,3,5,6-TETRAFLUOROBENZENESULFONAMIDE'>V50</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ht2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht2 OCA], [http://pdbe.org/4ht2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ht2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ht2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ht2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:[http://omim.org/entry/143860 143860]]. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.<ref>PMID:21035102</ref> | [[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:[http://omim.org/entry/143860 143860]]. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.<ref>PMID:21035102</ref> | ||
| - | + | == Function == | |
| - | ==Function== | + | |
[[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Reversible hydration of carbon dioxide. | [[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Reversible hydration of carbon dioxide. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented. | ||
| + | |||
| + | 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.,Dudutiene V, Zubriene A, Smirnov A, Gylyte J, Timm D, Manakova E, Grazulis S, Matulis D Bioorg Med Chem. 2013 Apr 1;21(7):2093-106. doi: 10.1016/j.bmc.2013.01.008. Epub , 2013 Jan 16. PMID:23394791<ref>PMID:23394791</ref> | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 4ht2" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | <references | + | *[[Carbonic anhydrase|Carbonic anhydrase]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
| - | [[Category: | + | [[Category: Human]] |
| - | [[Category: Grazulis, S | + | [[Category: Grazulis, S]] |
| - | [[Category: Manakova, E | + | [[Category: Manakova, E]] |
| - | [[Category: Smirnov, A | + | [[Category: Smirnov, A]] |
[[Category: Benzenesulfonamide]] | [[Category: Benzenesulfonamide]] | ||
[[Category: Carbon-oxygen lyase activity]] | [[Category: Carbon-oxygen lyase activity]] | ||
Revision as of 12:37, 4 August 2016
Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.
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