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| | ==Crystal structure of human carbonic anhydrase isozyme XII with 4-Propylthiobenzenesulfonamide== | | ==Crystal structure of human carbonic anhydrase isozyme XII with 4-Propylthiobenzenesulfonamide== |
| - | <StructureSection load='4ww8' size='340' side='right' caption='[[4ww8]], [[Resolution|resolution]] 1.42Å' scene=''> | + | <StructureSection load='4ww8' size='340' side='right'caption='[[4ww8]], [[Resolution|resolution]] 1.42Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ww8]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WW8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ww8]] 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=4WW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WW8 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=VD9:4-(PROPYLSULFANYL)BENZENESULFONAMIDE'>VD9</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]] 1.42Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wr7|4wr7]], [[4wup|4wup]], [[4wuq|4wuq]], [[4ww6|4ww6]]</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=VD9:4-(PROPYLSULFANYL)BENZENESULFONAMIDE'>VD9</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=4ww8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ww8 OCA], [https://pdbe.org/4ww8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ww8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ww8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ww8 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=4ww8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ww8 OCA], [http://pdbe.org/4ww8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ww8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ww8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ww8 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 == |
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| | ==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: Grazulis, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Manakova, E]] | + | [[Category: Grazulis S]] |
| - | [[Category: Smirnov, A]] | + | [[Category: Manakova E]] |
| - | [[Category: Benzenesulfonamide]] | + | [[Category: Smirnov A]] |
| - | [[Category: Carbonic anhydrase]]
| + | |
| - | [[Category: Drug design]]
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| - | [[Category: Lyase]]
| + | |
| - | [[Category: Lyase-lyase inhibitor comple]]
| + | |
| - | [[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
Para substituted tetrafluorobenzenesulfonamides bind to carbonic anhydrases (CAs) extremely tightly and exhibit some of the strongest known protein-small ligand interactions, reaching an intrinsic affinity of 2 pM as determined by displacement isothermal titration calorimetry (ITC). The enthalpy and entropy of binding to five CA isoforms were measured by ITC in two buffers of different protonation enthalpies. The pKa values of compound sulfonamide groups were measured potentiometrically and spectrophotometrically, and enthalpies of protonation were measured by ITC in order to evaluate the proton linkage contributions to the observed binding thermodynamics. Intrinsic means the affinity of a sulfonamide anion for the Zn bound water form of CAs. Fluorination of the benzene ring significantly enhanced the observed affinities as it increased the fraction of deprotonated ligand while having little impact on intrinsic affinities. Intrinsic enthalpy contributions to the binding affinity were dominant over entropy and were more exothermic for CA I than for other CA isoforms. Thermodynamic measurements together with the X-ray crystallographic structures of protein-ligand complexes enabled analysis of structure-activity relationships in this enzyme ligand system.
Intrinsic thermodynamics of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamide binding to carbonic anhydrases by isothermal titration calorimetry.,Zubriene A, Smirnoviene J, Smirnov A, Morkunaite V, Michailoviene V, Jachno J, Juozapaitiene V, Norvaisas P, Manakova E, Grazulis S, Matulis D Biophys Chem. 2015 Jun 6;205:51-65. doi: 10.1016/j.bpc.2015.05.009. PMID:26079542[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
- ↑ Zubriene A, Smirnoviene J, Smirnov A, Morkunaite V, Michailoviene V, Jachno J, Juozapaitiene V, Norvaisas P, Manakova E, Grazulis S, Matulis D. Intrinsic thermodynamics of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamide binding to carbonic anhydrases by isothermal titration calorimetry. Biophys Chem. 2015 Jun 6;205:51-65. doi: 10.1016/j.bpc.2015.05.009. PMID:26079542 doi:http://dx.doi.org/10.1016/j.bpc.2015.05.009
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