View source for 7qgx


==Human carbonic anhydrase II in complex with 3-((5-chloro-4-(4-chlorophenyl)thiazol-2-yl)(4-sulfamoylphenyl)amino)propanoic acid==
<StructureSection load='7qgx' size='340' side='right'caption='[[7qgx]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qgx]] 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=7QGX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QGX 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]] 1.19&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D85:3-[[5-chloranyl-4-(4-chlorophenyl)-1,3-thiazol-2-yl]-(4-sulfamoylphenyl)amino]propanoic+acid'>D85</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=7qgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qgx OCA], [https://pdbe.org/7qgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qgx RCSB], [https://www.ebi.ac.uk/pdbsum/7qgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qgx ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[https://omim.org/entry/259730 259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A series of novel benzenesulfonamide derivatives were synthesized bearing para-N beta,gamma-amino acid or para-N beta-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals. However, most of them bind to most CA isozymes with little selectivity. The design of high affinity and selectivity towards one CA isozyme remains a significant challenge. The beta and gamma amino acid-substituted compound affinities were determined by the fluorescent thermal shift assay and isothermal titration calorimetry for all 12 catalytically active human carbonic anhydrase isozymes, showing the full affinity and selectivity profile. The structures of several compounds were determined by X-ray crystallography, and the binding mode in the active site of CA enzyme was shown.

Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases.,Balandis B, Simkunas T, Paketuryte-Latve V, Michailoviene V, Mickeviciute A, Manakova E, Grazulis S, Belyakov S, Kairys V, Mickevicius V, Zubriene A, Matulis D Pharmaceuticals (Basel). 2022 Apr 13;15(4). pii: ph15040477. doi:, 10.3390/ph15040477. PMID:35455474<ref>PMID:35455474</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qgx" 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: Paketuryte-Latve V]]
[[Category: Smirnov A]]