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| | <StructureSection load='4qjx' size='340' side='right'caption='[[4qjx]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='4qjx' size='340' side='right'caption='[[4qjx]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qjx]] is a 1 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=4QJX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QJX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qjx]] is a 1 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=4QJX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QJX 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=WWO:3-(BENZYLAMINO)-2,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>WWO</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" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=WWO:3-(BENZYLAMINO)-2,5,6-TRIFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>WWO</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">[[4qiy|4qiy]], [[4qiz|4qiz]], [[4qj0|4qj0]], [[4qjm|4qjm]], [[4qjo|4qjo]], [[4qjp|4qjp]], [[4qjw|4qjw]], [[4qtl|4qtl]]</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=4qjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qjx OCA], [https://pdbe.org/4qjx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qjx RCSB], [https://www.ebi.ac.uk/pdbsum/4qjx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qjx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA13 ([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=4qjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qjx OCA], [http://pdbe.org/4qjx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qjx RCSB], [http://www.ebi.ac.uk/pdbsum/4qjx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qjx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CAH13_HUMAN CAH13_HUMAN]] Reversible hydration of carbon dioxide. | + | [https://www.uniprot.org/uniprot/CAH13_HUMAN CAH13_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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carbonate dehydratase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Grazulis, S]] | + | [[Category: Grazulis S]] |
| - | [[Category: Manakova, E]] | + | [[Category: Manakova E]] |
| - | [[Category: Smirnov, A]] | + | [[Category: Smirnov A]] |
| - | [[Category: Benzenesulfonamide]]
| + | |
| - | [[Category: Carbonic anhydrase]]
| + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| Structural highlights
Function
CAH13_HUMAN Reversible hydration of carbon dioxide.
Publication Abstract from PubMed
Substituted tri- and tetrafluorobenzenesulfonamides were designed, synthesized, and evaluated as high-affinity and isoform-selective carbonic anhydrase (CA) inhibitors. Their binding affinities for recombinant human CA I, II, VA, VI, VII, XII, and XIII catalytic domains were determined by fluorescent thermal shift assay, isothermal titration calorimetry, and a stopped-flow CO2 hydration assay. Variation of the substituents at the 2-, 3-, and 4-positions yielded compounds with a broad range of binding affinities and isoform selectivities. Several 2,4-substituted-3,5,6-trifluorobenzenesulfonamides were effective CA XIII inhibitors with high selectivity over off-target CA I and CA II. 3,4-Disubstituted-2,5,6-trifluorobenzenesulfonamides bound CAs with higher affinity than 2,4-disubstituted-3,5,6-trifluorobenzenesulfonamides. Many such fluorinated benzenesulfonamides were found to be nanomolar inhibitors of CA II, CA VII, tumor-associated CA IX and CA XII, and CA XIII. X-ray crystal structures of inhibitors bound in the active sites of several CA isoforms provide structure-activity relationship information for inhibitor binding affinities and selectivity.
Functionalization of Fluorinated Benzenesulfonamides and Their Inhibitory Properties toward Carbonic Anhydrases.,Dudutiene V, Zubriene A, Smirnov A, Timm DD, Smirnoviene J, Kazokaite J, Michailoviene V, Zaksauskas A, Manakova E, Grazulis S, Matulis D ChemMedChem. 2015 Apr;10(4):662-87. doi: 10.1002/cmdc.201402490. Epub 2015 Mar, 10. PMID:25758852[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dudutiene V, Zubriene A, Smirnov A, Timm DD, Smirnoviene J, Kazokaite J, Michailoviene V, Zaksauskas A, Manakova E, Grazulis S, Matulis D. Functionalization of Fluorinated Benzenesulfonamides and Their Inhibitory Properties toward Carbonic Anhydrases. ChemMedChem. 2015 Apr;10(4):662-87. doi: 10.1002/cmdc.201402490. Epub 2015 Mar, 10. PMID:25758852 doi:http://dx.doi.org/10.1002/cmdc.201402490
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