6oe0: Difference between revisions

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-'''Unreleased structure'''
-The entry 6oe0 is ON HOLD  until Paper Publication
+==Benzensulfonamides bearing spyrohydantoin moieties act as potent inhibitors of human carbonic anhydrases II and VII and show neuropathic pain attenuating effects==
+<StructureSection load='6oe0' size='340' side='right'caption='[[6oe0]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6oe0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OE0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OE0 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M8S:2-(2,4-dioxo-1,3-diazaspiro[4.6]undecan-3-yl)-N-(4-sulfamoylphenyl)acetamide'>M8S</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=6oe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oe0 OCA], [http://pdbe.org/6oe0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oe0 RCSB], [http://www.ebi.ac.uk/pdbsum/6oe0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oe0 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 ==
+Carbonic Anhydrases have been recently validated as novel therapeutic targets in neuropathic pain. In this study, we combine the anticonvulsant propriety of spyrohydantoin and the CA inhibitor moiety of benzenesulfonamide to synthesize a novel series of spyrohydantoin bearing sulfonamides with strong activity against hCA II and VII. These isoforms are present in the nervous system and largely expressed both at the central as well as at peripheral level and can be modulated for pain relief. The crystal structures of hCA II in complex with selected compounds 5a-c demonstrate the importance of the tail in the binding modes within the isoform. Finally, in vivo, in an animal model of oxaliplatin induced neuropathy, compounds with organoselenium tails (8b-c) showed potent neuropathic pain attenuating effects. Taken together, these data strongly suggest the translational utility of these inhibitors as novel pain relievers.
-Authors: Peat, T.S.
+Benzensulfonamides bearing spyrohydantoin moieties act as potent inhibitors of human carbonic anhydrases II and VII and show neuropathic pain attenuating effects.,Angeli A, Di Cesare Mannelli L, Ghelardini C, Peat TS, Bartolucci G, Menicatti M, Carta F, Supuran CT Eur J Med Chem. 2019 May 21;177:188-197. doi: 10.1016/j.ejmech.2019.05.058. PMID:31136893<ref>PMID:31136893</ref>
-Description: Benzensulfonamides bearing spyrohydantoin moieties act as potent inhibitors of human carbonic anhydrases II and VII and show neuropathic pain attenuating effects
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Peat, T.S]]
+<div class="pdbe-citations 6oe0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Carbonate dehydratase]]
+[[Category: Large Structures]]
+[[Category: Peat, T S]]
+[[Category: Carbonic anhydrase inhibitor]]
+[[Category: Lyase-lyase inhibitor complex]]
+[[Category: Metalloenzyme]]
+[[Category: Organoselenium]]