View source for 9g38


==CRYSTAL STRUCTURE OF HUMAN CARBONIC ANHYDRASE II IN COMPLEX WITH SALVIANOLIC ACID P==
<StructureSection load='9g38' size='340' side='right'caption='[[9g38]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9g38]] 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=9G38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9G38 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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IH2:(2~{S},3~{S})-3-[3,4-bis(oxidanyl)phenyl]-6-[(~{E})-3-[(2~{R})-3-[3,4-bis(oxidanyl)phenyl]-1-oxidanyl-1-oxidanylidene-propan-2-yl]oxy-3-oxidanylidene-prop-1-enyl]-2,3-dihydro-1,4-benzodioxine-2-carboxylic+acid'>A1IH2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=9g38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9g38 OCA], [https://pdbe.org/9g38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9g38 RCSB], [https://www.ebi.ac.uk/pdbsum/9g38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9g38 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> 
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== Publication Abstract from PubMed ==
In this study, four depsides were isolated from Origanum dictamnus L. and Satureja pilosa Velen. medicinal plants and their structures were assessed by means of one-dimensional (1D)- and two-dimensional (2D)-nuclear magnetic resonance, high resolution mass spectrometry, and electronic circular dichroism analyses. The compound 1, herein reported for the first time, salvianolic acid P 2, clinopodic acid I 3, and clinopodic acid O 4 were all profiled in vitro on a panel of human (h) expressed carbonic anhydrases (CAs; EC 4.2.1.1) and preferential inhibition for the tumor-associated human carbonic anhydrase (hCA) IX and hCA XII over the constitutively expressed hCA I and hCA II isoforms was observed. X-ray crystallography allowed us to assess the binding mode of salvianolic acid P 2 to hCA II. The compounds exhibited significant cytotoxic effects on the human triple-negative breast cancer cell line MDA-MB-231, suggesting that this class of depsides are promising molecules for future investigation.

Depsides from Origanum dictamnus and Satureja pilosa as selective inhibitors of carbonic anhydrases: Isolation, structure elucidation, X-ray crystallography.,Paloukopoulou C, Ntagli OS, Gherardi L, Dourdouni V, Filippou G, Alterio V, Giovannuzzi S, Massardi ML, De Simone G, Ronca R, Supuran CT, Pescitelli G, Karioti A Arch Pharm (Weinheim). 2025 Jan;358(1):e2400823. doi: 10.1002/ardp.202400823. PMID:39711099<ref>PMID:39711099</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 9g38" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alterio V]]
[[Category: De Simone G]]