4kp5: Difference between revisions
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==Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide== | ==Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide== | ||
<StructureSection load='4kp5' size='340' side='right' caption='[[4kp5]], [[Resolution|resolution]] 1.45Å' scene=''> | <StructureSection load='4kp5' size='340' side='right' caption='[[4kp5]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4kp5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4kp5]] 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=4KP5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KP5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E1F:2-CHLORO-4-[(PYRIMIDIN-2-YLSULFANYL)ACETYL]BENZENESULFONAMIDE'>E1F</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E1F:2-CHLORO-4-[(PYRIMIDIN-2-YLSULFANYL)ACETYL]BENZENESULFONAMIDE'>E1F</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kni|4kni]], [[4knj|4knj]], [[4knm|4knm]], [[4knn|4knn]], [[4kp8|4kp8]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kni|4kni]], [[4knj|4knj]], [[4knm|4knm]], [[4knn|4knn]], [[4kp8|4kp8]]</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 | <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='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=4kp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kp5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kp5 RCSB], [http://www.ebi.ac.uk/pdbsum/4kp5 PDBsum]</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=4kp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kp5 OCA], [http://pdbe.org/4kp5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kp5 RCSB], [http://www.ebi.ac.uk/pdbsum/4kp5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kp5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4kp5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Grazulis, S]] | [[Category: Grazulis, S]] | ||
[[Category: Manakova, E]] | [[Category: Manakova, E]] | ||
Revision as of 19:23, 11 August 2016
Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamideCrystal structure of catalytic domain of human carbonic anhydrase isozyme XII with 2-Chloro-4-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide
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 PubMedTwo groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms. Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII.,Capkauskaite E, Zubriene A, Smirnov A, Torresan J, Kisonaite M, Kazokaite J, Gylyte J, Michailoviene V, Jogaite V, Manakova E, Grazulis S, Tumkevicius S, Matulis D Bioorg Med Chem. 2013 Nov 15;21(22):6937-47. doi: 10.1016/j.bmc.2013.09.029. Epub, 2013 Sep 20. PMID:24103428[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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