6qn2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6qn2' size='340' side='right'caption='[[6qn2]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='6qn2' size='340' side='right'caption='[[6qn2]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6qn2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[6qn2]] 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=6QN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QN2 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=J92:methyl+4-[(4-chloranyl-2-cyclohexylsulfanyl-5-sulfamoyl-phenyl)carbonylamino]butanoate'>J92</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=6qn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qn2 OCA], [https://pdbe.org/6qn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qn2 RCSB], [https://www.ebi.ac.uk/pdbsum/6qn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qn2 ProSAT]</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=6qn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qn2 OCA], [https://pdbe.org/6qn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qn2 RCSB], [https://www.ebi.ac.uk/pdbsum/6qn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qn2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 27: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Leitans | [[Category: Leitans J]] | ||
[[Category: Tars | [[Category: Tars K]] | ||
Revision as of 15:04, 24 January 2024
Three dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamideThree dimensional structure of human carbonic anhydrase IX in complex with benzenesulfonamide
Structural highlights
FunctionCAH9_HUMAN Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.[1] Publication Abstract from PubMedBy applying an approach of a "ring with two tails", a series of novel inhibitors possessing high-affinity and significant selectivity towards selected carbonic anhydrase (CA) isoforms has been designed. The "ring" consists of 2-chloro/bromo-benzenesulfonamide, where the sulfonamide group is as an anchor coordinating the Zn(II) in the active site of CAs, and halogen atom orients the ring affecting the affinity and selectivity. First "tail" is a substituent containing carbonyl, carboxyl, hydroxyl, ether groups or hydrophilic amide linkage. The second "tail" contains aryl- or alkyl-substituents attached through a sulfanyl or sulfonyl group. Both "tails" are connected to the benzene ring and play a crucial role in selectivity. Varying the substituents, we designed compounds selective for CA VII, CA IX, CA XII, or CA XIV. Since due to binding-linked protonation reactions the binding-ready fractions of the compound and protein are much lower than one, the "intrinsic" affinities were calculated that should be used to study correlations between crystal structures and the thermodynamics of binding for rational drug design. The "intrinsic" affinities together with the intrinsic enthalpies and entropies of binding together with co-crystal structures were used demonstrate structural factors determining major contributions for compound affinity and selectivity. Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms.,Zaksauskas A, Capkauskaite E, Jezepcikas L, Linkuviene V, Paketuryte V, Smirnov A, Leitans J, Kazaks A, Dvinskis E, Manakova E, Grazulis S, Tars K, Matulis D Eur J Med Chem. 2020 Jan 1;185:111825. doi: 10.1016/j.ejmech.2019.111825. Epub, 2019 Oct 31. PMID:31740053[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||