7jo0: Difference between revisions

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 ==Carbonic Anhydrase IX Mimic Complexed with N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propionamide==
-<StructureSection load='7jo0' size='340' side='right'caption='[[7jo0]]' scene=''>
+<StructureSection load='7jo0' size='340' side='right'caption='[[7jo0]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JO0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JO0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7jo0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JO0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JO0 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7jo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jo0 OCA], [http://pdbe.org/7jo0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jo0 RCSB], [http://www.ebi.ac.uk/pdbsum/7jo0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jo0 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=VFG:N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide'>VFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://proteopedia.org/fgij/fg.htm?mol=7jo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jo0 OCA], [http://pdbe.org/7jo0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jo0 RCSB], [http://www.ebi.ac.uk/pdbsum/7jo0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jo0 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 ==
+This study provides a structure-activity relationship study of a series of lipophilic carbonic anhydrase (CA) inhibitors with an acetazolamide backbone. The inhibitors were tested against the tumor-expressed CA isozyme IX (CA IX), and the cytosolic CA I, CA II, and membrane-bound CA IV. The study identified several low nanomolar potent inhibitors against CA IX, with lipophilicities spanning two log units. Very potent pan-inhibitors with nanomolar potency against CA IX and sub-nanomolar potency against CA II and CA IV, and with potency against CA I one order of magnitude better than the parent acetazolamide 1 were also identified in this study, together with compounds that displayed selectivity against membrane-bound CA IV. A comprehensive X-ray crystallographic study (12 crystal structures), involving both CA II and a soluble CA IX mimetic (CA IX-mimic), revealed the structural basis of this particular inhibition profile and laid the foundation for further developments toward more potent and selective inhibitors for the tumor-expressed CA IX.
+Structural Basis of Nanomolar Inhibition of Tumor-Associated Carbonic Anhydrase IX: X-Ray Crystallographic and Inhibition Study of Lipophilic Inhibitors with Acetazolamide Backbone.,Andring JT, Fouch M, Akocak S, Angeli A, Supuran CT, Ilies MA, McKenna R J Med Chem. 2020 Oct 21. doi: 10.1021/acs.jmedchem.0c01390. PMID:33085484<ref>PMID:33085484</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7jo0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Carbonate dehydratase]]
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Andring JT]]
+[[Category: Andring, J T]]
-[[Category: McKenna R]]
+[[Category: McKenna, R]]
+[[Category: Ca inhibitor]]
+[[Category: Caii]]
+[[Category: Caix]]
+[[Category: Carbonic anhydrase]]
+[[Category: Carbonic anhydrase ii]]
+[[Category: Carbonic anhydrase ix]]
+[[Category: Lyase]]
+[[Category: Lyase-inhibitor complex]]
+[[Category: Structure guided drug design]]
+[[Category: Sulfonamide]]