View source for 6f3b


==Crystal structure of human carbonic anhydrase I in complex with the 1-(2-hydroxy-5-sulfamoylphenyl)-3-[(4-methylphenyl)methyl]urea inhibitor==
<StructureSection load='6f3b' size='340' side='right' caption='[[6f3b]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6f3b]] is a 2 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=6F3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F3B FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CJK:1-[(4-methylphenyl)methyl]-3-(2-oxidanyl-5-sulfamoyl-phenyl)urea'>CJK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[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=6f3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f3b OCA], [http://pdbe.org/6f3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f3b RCSB], [http://www.ebi.ac.uk/pdbsum/6f3b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f3b ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CAH1_HUMAN CAH1_HUMAN]] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.<ref>PMID:10550681</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Herein we report the 2-aminophenol-4-sulfonamide 1 and its ureido derivatives 2-23 as inhibitors of the carbonic anhydrase (CA, EC 4.2.1.1) enzymes as analogues of the hypoxic tumor phase II entering drug SLC-0111. This scaffold may determine preferential rotational isomers to selectively interact within the tumor-associated CAs. Most of the compounds indeed showed in vitro selective inhibition of the tumor associated CA isoforms IX and XII. The most potent derivative within the series was 11 ( KIs of 2.59 and 7.64 nM on hCA IX and XII, respectively), which shares the 4-fluorophenylureido tail with the clinical candidate. We investigated by means of X-ray crystallographic studies the binding modes of three selected compounds of this series to CA I. The evaluation of therapeutic efficacy of compound 11 in an orthotopic, syngeneic model of CA IX-positive breast cancer in vivo showed close matching antitumoral effects and tolerance with SLC-0111.

Discovery of 4-Hydroxy-3-(3-(phenylureido)benzenesulfonamides as SLC-0111 Analogues for the Treatment of Hypoxic Tumors Overexpressing Carbonic Anhydrase IX.,Bozdag M, Carta F, Ceruso M, Ferraroni M, McDonald PC, Dedhar S, Supuran CT J Med Chem. 2018 Jul 26;61(14):6328-6338. doi: 10.1021/acs.jmedchem.8b00770. Epub, 2018 Jul 17. PMID:29962205<ref>PMID:29962205</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6f3b" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carbonate dehydratase]]
[[Category: Homo sapiens]]
[[Category: Bozdag, M]]
[[Category: Chiapponi, D]]
[[Category: Ferraroni, M]]
[[Category: Supuran, C T]]
[[Category: Lyase]]