4ww8: Difference between revisions
New page: '''Unreleased structure''' The entry 4ww8 is ON HOLD Authors: Smirnov, A., Manakova, E., Grazulis, S. Description: Crystal structure of human carbonic anhydrase isozyme XII with 4-Prop... |
No edit summary |
||
| (7 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==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=''> | |||
== Structural highlights == | |||
<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='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='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='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> | |||
</table> | |||
== Disease == | |||
[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 == | |||
[https://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN] Reversible hydration of carbon dioxide. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:26079542</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ww8" style="background-color:#fffaf0;"></div> | |||
==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 13:44, 10 January 2024
Crystal structure of human carbonic anhydrase isozyme XII with 4-PropylthiobenzenesulfonamideCrystal structure of human carbonic anhydrase isozyme XII with 4-Propylthiobenzenesulfonamide
Structural highlights
DiseaseCAH12_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] FunctionCAH12_HUMAN Reversible hydration of carbon dioxide. Publication Abstract from PubMedPara 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 AlsoReferences
|
| ||||||||||||||||||