4qiz: Difference between revisions
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==Crystal structure of human carbonic anhydrase isozyme XIII with inhibitor== | |||
<StructureSection load='4qiz' size='340' side='right'caption='[[4qiz]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4qiz]] is a 2 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=4QIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QIZ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</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=WWX:2,3,6-TRIFLUORO-5-{[(1R,2S)-2-HYDROXY-1,2-DIPHENYLETHYL]AMINO}-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>WWX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4qiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qiz OCA], [https://pdbe.org/4qiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qiz RCSB], [https://www.ebi.ac.uk/pdbsum/4qiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qiz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH13_HUMAN CAH13_HUMAN] Reversible hydration of carbon dioxide. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:25758852</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4qiz" style="background-color:#fffaf0;"></div> | ||
[[Category: Grazulis | |||
[[Category: Smirnov | ==See Also== | ||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Grazulis S]] | |||
[[Category: Manakova E]] | |||
[[Category: Smirnov A]] | |||
Latest revision as of 18:06, 8 November 2023
Crystal structure of human carbonic anhydrase isozyme XIII with inhibitorCrystal structure of human carbonic anhydrase isozyme XIII with inhibitor
Structural highlights
FunctionCAH13_HUMAN Reversible hydration of carbon dioxide. Publication Abstract from PubMedSubstituted 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 AlsoReferences
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