8cr0

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m (Protected "8cr0" [edit=sysop:move=sysop])
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'''Unreleased structure'''
 
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The entry 8cr0 is ON HOLD until Paper Publication
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==Crystal structure of human carbonic anhydrase II in complex with a triazolyl benzoxaborole inhibitor==
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<StructureSection load='8cr0' size='340' side='right'caption='[[8cr0]], [[Resolution|resolution]] 1.22&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8cr0]] 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=8CR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CR0 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=VI6:1-[1,1-bis(oxidanyl)-3~{H}-2,1$l^{4}-benzoxaborol-6-yl]-4-[(4-fluoranylphenoxy)methyl]-1,2,3-triazole'>VI6</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cr0 OCA], [https://pdbe.org/8cr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cr0 RCSB], [https://www.ebi.ac.uk/pdbsum/8cr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cr0 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Benzoxaborole is currently a scaffold of great relevance in medicinal chemistry. In 2016, it was reported to be a new and valuable chemotype for designing carbonic anhydrase (CA) inhibitors. Herein, using an in silico design, we report the synthesis and characterization of substituted 6-(1H-1,2,3-triazol-1-yl)benzoxaboroles. 6-Azidobenzoxaborole was described for the first time as a molecular platform to prepare libraries of inhibitors by a copper(I)-catalyzed azide-alkyne cycloaddition via a click chemistry strategy. With inhibition constants below 30 nM, some derivatives, such as compound 20, showed efficacy as selective hCA VII and IX inhibitors. The design hypothesis was validated by crystallographic investigation on the hCA II/20 adduct, which provided explanations over the different inhibition behavior observed against the five evaluated hCA isoforms. Overall, this study identified 20 as a new promising lead compound to develop novel anticancer agents targeting the tumor-associated hCA IX but also potent neuropathic pain relievers targeting hCA VII.
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Authors: Alterio, V., De Simone, G., Esposito, D.
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6-Substituted Triazolyl Benzoxaboroles as Selective Carbonic Anhydrase Inhibitors: In Silico Design, Synthesis, and X-ray Crystallography.,Nocentini A, Bonardi A, Bazzicalupi C, Alterio V, Esposito D, Monti SM, Smietana M, De Simone G, Supuran CT, Gratteri P, Winum JY J Med Chem. 2023 Jun 7. doi: 10.1021/acs.jmedchem.3c00433. PMID:37283561<ref>PMID:37283561</ref>
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Description: Crystal structure of human carbonic anhydrase II in complex with a triazolyl benzoxaborole inhibitor
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Esposito, D]]
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<div class="pdbe-citations 8cr0" style="background-color:#fffaf0;"></div>
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[[Category: Alterio, V]]
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== References ==
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[[Category: De Simone, G]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Alterio V]]
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[[Category: De Simone G]]
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[[Category: Esposito D]]

Revision as of 09:37, 21 June 2023

Crystal structure of human carbonic anhydrase II in complex with a triazolyl benzoxaborole inhibitor

PDB ID 8cr0

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