5e2r: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==The crystal structure of the human carbonic anhydrase II in complex with a 1,1'-biphenyl-4-sulfonamide inhibitor==
+<StructureSection load='5e2r' size='340' side='right' caption='[[5e2r]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5e2r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E2R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E2R FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=520:4-(4-AMINOBENZOYL)BIPHENYL-4-SULFONAMIDE'>520</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">[[5cjf|5cjf]]</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=5e2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2r OCA], [http://pdbe.org/5e2r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e2r RCSB], [http://www.ebi.ac.uk/pdbsum/5e2r 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 ==
+New 1,1'-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1-21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1'-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.
-The entry 5e2r is ON HOLD  until Paper Publication
+Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors.,La Regina G, Coluccia A, Famiglini V, Pelliccia S, Monti L, Vullo D, Nuti E, Alterio V, De Simone G, Monti SM, Pan P, Parkkila S, Supuran CT, Rossello A, Silvestri R J Med Chem. 2015 Nov 12;58(21):8564-72. doi: 10.1021/acs.jmedchem.5b01144. Epub, 2015 Nov 4. PMID:26497049<ref>PMID:26497049</ref>
-Authors: Alterio, V., De Simone, G.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: The crystal structure of the human carbonic anhydrase II in complex with a 1,1'-biphenyl-4-sulfonamide inhibitor
+<div class="pdbe-citations 5e2r" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: De Simone, G]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Carbonate dehydratase]]
 [[Category: Alterio, V]]
+[[Category: Simone, G De]]
+[[Category: 1'-biphenyl-4-sulfonamide]]
+[[Category: Complex]]
+[[Category: Inhibitor]]
+[[Category: Lyase]]