View source for 3eft


==Crystal structure of the complex between Carbonic Anhydrase II and a spin-labeled sulfonamide incorporating TEMPO moiety==
<StructureSection load='3eft' size='340' side='right'caption='[[3eft]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3eft]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EFT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BS:3-CHLORO-4-{[(1-HYDROXY-2,2,6,6-TETRAMETHYLPIPERIDIN-4-YL)CARBAMOTHIOYL]AMINO}BENZENESULFONAMIDE'>3BS</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3eft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eft OCA], [https://pdbe.org/3eft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eft RCSB], [https://www.ebi.ac.uk/pdbsum/3eft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eft 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/ef/3eft_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3eft ConSurf].
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== Publication Abstract from PubMed ==
Spin-labeled sulfonamides incorporating TEMPO moieties showed efficient activity as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and, in particular, of the physiologically relevant isoenzymes hCA II, hCA IX, and hCA XIV. Here we report a detailed analysis of this class of inhibitors by means of ESR and X-ray crystallography, in comparison with inhibition tests against all mammalian CA isoforms, CA I-XIV. Local dynamics and structure were manifested in the ESR signal through modulation of internal magnetic anisotropies. Analysis and fitting of the ESR spectra of several spin-labeled sulfonamides with isoforms CA II (cytosolic), CA IX (catalytic domain and full length transmembrane, tumor-associated isoform) and CA XIV (transmembrane isozyme) provided information about polarity and dynamics of specific microenvironments sensed by the nitroxyl group within the active site cavity of these isozymes. The comparison of ESR and crystallographic data of hCA II complexed with one of these inhibitors constitutes a useful tool for the understanding of molecular hindrance and ordering within the enzyme active site, and provides theoretical bases to use these inhibitors for imaging purposes of hypoxic tumors overexpressing the transmembrane isozyme CA IX. Combining the sulfonamide zinc-binding group with the TEMPO moiety thus allowed to dissect the selective inhibition mechanism of different cytosolic and transmembrane carbonic anhydrases.

Dissecting the Inhibition Mechanism of Cytosolic versus Transmembrane Carbonic Anhydrases by ESR.,Ciani L, Cecchi A, Temperini C, Supuran CT, Ristori S J Phys Chem B. 2009 Oct 22;113(42):13998-4005. PMID:19778001<ref>PMID:19778001</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 3eft" style="background-color:#fffaf0;"></div>

==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Large Structures]]
[[Category: Cecchi, A]]
[[Category: Scozzafava, A]]
[[Category: Supuran, C T]]
[[Category: Temperini, C]]
[[Category: Carbonic anhydrase]]
[[Category: Inhibitor]]
[[Category: Lyase]]
[[Category: Oxo-acid]]
[[Category: Radical]]