|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.== | | ==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=''> | + | <StructureSection load='4ht2' size='340' side='right'caption='[[4ht2]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == 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> | + | <table><tr><td colspan='2'>[[4ht2]] 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=4HT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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=4ht2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ht2 OCA], [https://pdbe.org/4ht2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ht2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ht2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ht2 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=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> | | </table> |
| | == Disease == | | == 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> | + | [https://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN] Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:[https://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. | + | [https://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN] Reversible hydration of carbon dioxide. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Carbonic anhydrase|Carbonic anhydrase]] | + | *[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carbonate dehydratase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Grazulis, S]] | + | [[Category: Grazulis S]] |
| - | [[Category: Manakova, E]] | + | [[Category: Manakova E]] |
| - | [[Category: Smirnov, A]] | + | [[Category: Smirnov A]] |
| - | [[Category: Benzenesulfonamide]]
| + | |
| - | [[Category: Carbon-oxygen lyase activity]]
| + | |
| - | [[Category: Carbonate dehydratase activity]]
| + | |
| - | [[Category: Carbonic anhydrase]]
| + | |
| - | [[Category: Catalytic activity]]
| + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| Structural highlights
Disease
CAH12_HUMAN Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM: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.[1]
Function
CAH12_HUMAN Reversible hydration of carbon dioxide.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feldshtein M, Elkrinawi S, Yerushalmi B, Marcus B, Vullo D, Romi H, Ofir R, Landau D, Sivan S, Supuran CT, Birk OS. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. Am J Hum Genet. 2010 Nov 12;87(5):713-20. doi: 10.1016/j.ajhg.2010.10.008. Epub, 2010 Oct 28. PMID:21035102 doi:10.1016/j.ajhg.2010.10.008
- ↑ Dudutiene V, Zubriene A, Smirnov A, Gylyte J, Timm D, Manakova E, Grazulis S, Matulis D. 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem. 2013 Apr 1;21(7):2093-106. doi: 10.1016/j.bmc.2013.01.008. Epub , 2013 Jan 16. PMID:23394791 doi:http://dx.doi.org/10.1016/j.bmc.2013.01.008
|
