7bg5: Difference between revisions
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==4-(2-(3-(4-iodophenyl)ureido)ethyl)benzenesulfonamide in complex with Carbonic Anhydrase II== | ==4-(2-(3-(4-iodophenyl)ureido)ethyl)benzenesulfonamide in complex with Carbonic Anhydrase II== | ||
<StructureSection load='7bg5' size='340' side='right'caption='[[7bg5]]' scene=''> | <StructureSection load='7bg5' size='340' side='right'caption='[[7bg5]], [[Resolution|resolution]] 1.43Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BG5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bg5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BG5 FirstGlance]. <br> | ||
</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=7bg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bg5 OCA], [https://pdbe.org/7bg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bg5 RCSB], [https://www.ebi.ac.uk/pdbsum/7bg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bg5 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TKQ:1-(4-iodophenyl)-3-[2-(4-sulfamoylphenyl)ethyl]urea'>TKQ</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'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7bg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bg5 OCA], [https://pdbe.org/7bg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bg5 RCSB], [https://www.ebi.ac.uk/pdbsum/7bg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bg5 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
Tegumental carbonic anhydrase from the worm Schistosoma mansoni (SmCA) is considered a new anti-parasitic target because suppressing its expression interferes with schistosome metabolism and virulence. Here, we present the inhibition profiles of selenoureido compounds on recombinant SmCA and resolution of the first X-ray crystal structures of SmCA in adduct with a selection of such inhibitors. The key molecular features of such compounds in adduct with SmCA were obtained and compared to the human isoform hCA II, in order to understand the main structural factors responsible for enzymatic affinity and selectivity. Compounds that more specifically inhibited the schistosome versus human enzymes were identified. The results expand current knowledge in the field and pave the way for the development of more potent antiparasitic agents in the near future. | |||
Structural Insights into Schistosoma mansoni Carbonic Anhydrase (SmCA) Inhibition by Selenoureido-Substituted Benzenesulfonamides.,Angeli A, Ferraroni M, Da'dara AA, Selleri S, Pinteala M, Carta F, Skelly PJ, Supuran CT J Med Chem. 2021 Jul 22;64(14):10418-10428. doi: 10.1021/acs.jmedchem.1c00840., Epub 2021 Jul 7. PMID:34232641<ref>PMID:34232641</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bg5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Angeli A]] | [[Category: Angeli, A]] | ||
[[Category: Ferraroni M]] | [[Category: Ferraroni, M]] | ||
[[Category: Carbonic anhydrase ii]] | |||
[[Category: Inhibitor]] | |||
[[Category: Lyase]] | |||
[[Category: Sulfonamide]] | |||