4fik: Difference between revisions
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==Human carbonic anhydrase II H64A complexed with thioxolone hydrolysis products== | ==Human carbonic anhydrase II H64A complexed with thioxolone hydrolysis products== | ||
<StructureSection load='4fik' size='340' side='right' caption='[[4fik]], [[Resolution|resolution]] 1.20Å' scene=''> | <StructureSection load='4fik' size='340' side='right' caption='[[4fik]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fik]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4fik]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iqk 3iqk]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FIK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D2S:4,4-DISULFANEDIYLDIBENZENE-1,3-DIOL'>D2S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TH0:4-MERCAPTOBENZENE-1,3-DIOL'>TH0</scene>, <scene name='pdbligand=TH7:2,4-DIHYDROXYBENZENESULFENIC+ACID'>TH7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D2S:4,4-DISULFANEDIYLDIBENZENE-1,3-DIOL'>D2S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TH0:4-MERCAPTOBENZENE-1,3-DIOL'>TH0</scene>, <scene name='pdbligand=TH7:2,4-DIHYDROXYBENZENESULFENIC+ACID'>TH7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2osf|2osf]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2osf|2osf]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=4fik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fik OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fik RCSB], [http://www.ebi.ac.uk/pdbsum/4fik PDBsum]</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=4fik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fik OCA], [http://pdbe.org/4fik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fik RCSB], [http://www.ebi.ac.uk/pdbsum/4fik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fik ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4fik" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Agbandje-McKenna, M]] | [[Category: Agbandje-McKenna, M]] | ||
[[Category: Genis, C]] | [[Category: Genis, C]] | ||
Revision as of 06:33, 5 August 2016
Human carbonic anhydrase II H64A complexed with thioxolone hydrolysis productsHuman carbonic anhydrase II H64A complexed with thioxolone hydrolysis products
Structural highlights
Disease[CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM: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.[1] [2] [3] [4] [5] Function[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.[6] [7] Publication Abstract from PubMedThioxolone acts as a prodrug in the presence of carbonic anhydrase II (CA II), whereby the molecule is cleaved by thioester hydrolysis to the carbonic anhydrase inhibitor, 4-mercaptobenzene-1,3-diol (TH0). Thioxolone was soaked into the proton transfer mutant H64A of CA II in an effort to capture a reaction intermediate via X-ray crystallography. Structure determination of the 1.2 A resolution data revealed the TH0 had been modified to a 4,4'-disulfanediyldibenzene-1,3-diol, a product of crystallization conditions, and a zinc ligated 2,4-dihydroxybenzenesulfenic acid, most likely induced by radiation damage. Neither ligand was likely a result of an enzymatic mechanism. Synchrotron Radiation Provides a Plausible Explanation for the Generation of a Free Radical Adduct of Thioxolone in Mutant Carbonic Anhydrase II.,Sippel KH, Genis C, Govindasamy L, Agbandje-McKenna M, Kiddle JJ, Tripp BC, McKenna R J Phys Chem Lett. 2010 Oct 7;1(19):2898-2902. PMID:20976122[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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