View source for 6got


==Crystal structure of human carbonic anhydrase II in complex with the inhibitor 4-(phenethylthio)benzenesulfonamide==
<StructureSection load='6got' size='340' side='right' caption='[[6got]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6got]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GOT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F6W:4-(2-phenylethylsulfanyl)benzenesulfonamide'>F6W</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6got FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6got OCA], [http://pdbe.org/6got PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6got RCSB], [http://www.ebi.ac.uk/pdbsum/6got PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6got ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN]] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[http://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 ==
[[http://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 ==
Several new molecules with different thio-scaffolds were designed, synthesised, and evaluated biologically as inhibitors of Carbonic Anhydrases (CAIs). The structure-activity relationship analysis identified thioether derivatives, here reported, as a potent and selective CAIs against hCA II and hCA IX. High resolution X-ray structure of inhibitor bound hCA II revealed extensive interactions with the hydrophobic pocket of active site and provided molecular insight into the binding properties of these new inhibitors.

Synthesis of different thio-scaffolds bearing sulfonamide with subnanomolar carbonic anhydrase II and IX inhibitory properties and X-ray investigations for their inhibitory mechanism.,Angeli A, Tanini D, Capperucci A, Malevolti G, Turco F, Ferraroni M, Supuran CT Bioorg Chem. 2018 Sep 20;81:642-648. doi: 10.1016/j.bioorg.2018.09.028. PMID:30253337<ref>PMID:30253337</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6got" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Homo sapiens]]
[[Category: Angeli, A]]
[[Category: Ferraroni, M]]
[[Category: Supuran, C T]]
[[Category: Lyase]]