View source for 3ibu


==The crystal structure of the human carbonic anhydrase II in complex with an aliphatic sulfamate inhibitor==
<StructureSection load='3ibu' size='340' side='right'caption='[[3ibu]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ibu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IBU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HGB:4-(HYDROXYMERCURY)BENZOIC+ACID'>HGB</scene>, <scene name='pdbligand=O48:DECYL+SULFAMATE'>O48</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3ibu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ibu OCA], [https://pdbe.org/3ibu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ibu RCSB], [https://www.ebi.ac.uk/pdbsum/3ibu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ibu ProSAT]</span></td></tr>
</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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ib/3ibu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ibu ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Two approaches were used to design inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): the tail and the ring approaches. Aliphatic sulfamates constitute a class of CA inhibitors (CAIs) that cannot be classified in either one of these categories. We report here the detailed inhibition profile of four such compounds against isoforms CAs I-XIV, the first crystallographic structures of these compounds in adduct with isoform II, and molecular modeling studies for their interaction with hCA IX. Aliphatic monosulfamates/bis-sulfamates were nanomolar inhibitors of hCAs II, IX, and XII, unlike aromatic/heterocyclic sulfonamides that promiscuously inhibit most CA isozymes with low nanomolar affinity. The bis-sulfamates incorporating 8 or 10 carbon atoms showed higher affinity for the tumor-associated hCA IX compared to hCA II, whereas the opposite was true for the monosulfamates. The explanation for their interaction with CA active site furnishes insights for obtaining compounds with increased affinity/selectivity for various isozymes.

Carbonic Anhydrase Inhibitors. Comparison of Aliphatic Sulfamate/Bis-sulfamate Adducts with Isozymes II and IX as a Platform for Designing Tight-Binding, More Isoform-Selective Inhibitors.,Vitale RM, Alterio V, Innocenti A, Winum JY, Monti SM, De Simone G, Supuran CT J Med Chem. 2009 Sep 4. PMID:19731956<ref>PMID:19731956</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3ibu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alterio V]]
[[Category: De Simone G]]