5fdc: Difference between revisions

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-'''Unreleased structure'''
-The entry 5fdc is ON HOLD  until Paper Publication
+==Crystal structure of Human Carbonic Anhydrase II in complex with the anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog.==
+<StructureSection load='5fdc' size='340' side='right' caption='[[5fdc]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5fdc]] 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=5FDC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FDC FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5WN:3-[(sulfamoylamino)methyl]-1-benzothiophene'>5WN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HGB:4-(HYDROXYMERCURY)BENZOIC+ACID'>HGB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ca2|1ca2]]</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=5fdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fdc OCA], [http://pdbe.org/5fdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fdc RCSB], [http://www.ebi.ac.uk/pdbsum/5fdc PDBsum]</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 ==
+JNJ-26990990 ((benzo[b]thien-3-yl)methyl)sulfamide, a sulfamide derivative structurally related to the antiepileptic drug zonisamide, was reported to be devoid of carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties. Here we report that JNJ-26990990 and its S,S-dioxide analog significantly inhibit six human (h) isoforms, hCA I, II, VII, IX, XII and XIV, involved in crucial physiological processes. Inhibition and X-ray crystallographic data for the binding of the two compounds to these enzymes show significant similarity with the zonisamide inhibitory pattern. These findings prompted us to reconsider the structural/pharmacological requirements for designing effective antiepileptics possessing zinc-binding groups of the sulfamide, sulfamate or sulfonamide type in their molecules.
-Authors: Di Fiore, A., De Simone, G., Alterio, V., Riccio, V., Winum, J.-Y., Carta, F., Supuran, C.T.
+The anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog strongly inhibit carbonic anhydrases: solution and X-ray crystallographic studies.,Di Fiore A, De Simone G, Alterio V, Riccio V, Winum JY, Carta F, Supuran CT Org Biomol Chem. 2016 Jun 7;14(21):4853-8. doi: 10.1039/c6ob00803h. Epub 2016 May, 6. PMID:27151329<ref>PMID:27151329</ref>
-Description: Crystal structure of Human Carbonic Anhydrase II in complex with the anticonvulsant sulfamide JNJ-26990990 and its S,S-dioxide analog.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Di Fiore, A]]
+<div class="pdbe-citations 5fdc" style="background-color:#fffaf0;"></div>
-[[Category: Winum, J.-Y]]
+== References ==
-[[Category: Supuran, C.T]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Carbonate dehydratase]]
+[[Category: Homo sapiens]]
+[[Category: Alterio, V]]
 [[Category: Carta, F]]
-[[Category: De Simone, G]]
+[[Category: Fiore, A Di]]
 [[Category: Riccio, V]]
-[[Category: Alterio, V]]
+[[Category: Simone, G De]]
+[[Category: Supuran, C T]]
+[[Category: Winum, J Y]]
+[[Category: Lyase]]
+[[Category: Protein-inhibitor complex]]
+[[Category: Sulfamide inhibitor]]