1xq0: Difference between revisions

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-{{Seed}}
-[[Image:1xq0.png|left|200px]]
-<!--
+==Structure of human carbonic anhydrase II with 4-[(3-bromo-4-O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]-triazole==
-The line below this paragraph, containing "STRUCTURE_1xq0", creates the "Structure Box" on the page.
+<StructureSection load='1xq0' size='340' side='right'caption='[[1xq0]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1xq0]] 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=1XQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XQ0 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4TR:2-BROMO-4-{[(4-CYANOPHENYL)(4H-1,2,4-TRIAZOL-4-YL)AMINO]METHYL}PHENYL+SULFAMATE'>4TR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_1xq0|  PDB=1xq0  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xq0 OCA], [https://pdbe.org/1xq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xq0 RCSB], [https://www.ebi.ac.uk/pdbsum/1xq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xq0 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/xq/1xq0_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=1xq0 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide to hydrogen carbonate. The role of CA in maintaining pH balance has made it an attractive drug target for the treatment of cancer, and it has recently been implicated in the delivery of sulfamate-containing drugs. With the acceptance of steroid sulfatase as a target for hormone-dependent cancer, novel dual aromatase-steroid sulfatase inhibitors (DASIs) containing a sulfamate group are now being developed. In this study, we show that CA II is potently inhibited by several members of this class of inhibitor. The structures of CA II complexed with 4-[(4-O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole (K(D) = 84 +/- 5 nM) and 4-[(3-bromo-4-O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole (K(D) = 454 +/- 29 nM) are reported to 2.02 and 1.76 A, respectively. Both inhibitors ligate to the active site zinc(II) atom via their sulfamate nitrogen, while the rest of the molecule is contained within the hydrophobic binding pocket. Key protein residues include Val-121, Phe-131, Val-135, Val-143, Leu-141, Leu-198, Pro-202, and Leu-204. Despite being structurally similar, the two ligands experience different types of binding particularly in the sulfamate-containing aromatic ring and the opposite geometric arrangement of the triazole and cyanophenyl groups around the configurationally invertible central nitrogen atom. Small changes in inhibitor structure can cause large changes in binding to CA II, and this underlines the importance of structure-based drug design with this enzyme and other isoforms relevant to potential anticancer therapy. Moreover, these results underpin the idea that binding to erythrocyte CA II may be a general method of stabilizing and delivering sulfamate-based drugs in vivo.
-===Structure of human carbonic anhydrase II with 4-[(3-bromo-4-O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]-triazole===
+First crystal structures of human carbonic anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors.,Lloyd MD, Thiyagarajan N, Ho YT, Woo LW, Sutcliffe OB, Purohit A, Reed MJ, Acharya KR, Potter BV Biochemistry. 2005 May 10;44(18):6858-66. PMID:15865431<ref>PMID:15865431</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1xq0" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15865431}}, adds the Publication Abstract to the page
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15865431 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15865431}}
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]]
-==About this Structure==
-XQ0 is a [[Single protein]] structure of 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=1XQ0 OCA].
-==Reference==
-First crystal structures of human carbonic anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors., Lloyd MD, Thiyagarajan N, Ho YT, Woo LW, Sutcliffe OB, Purohit A, Reed MJ, Acharya KR, Potter BV, Biochemistry. 2005 May 10;44(18):6858-66. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15865431 15865431]
-[[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Acharya, K R.]]
+[[Category: Acharya KR]]
-[[Category: Ho, Y T.]]
+[[Category: Ho YT]]
-[[Category: Lloyd, M D.]]
+[[Category: Lloyd MD]]
-[[Category: Potter, B V.L.]]
+[[Category: Potter BVL]]
-[[Category: Purohit, A.]]
+[[Category: Purohit A]]
-[[Category: Reed, M J.]]
+[[Category: Reed MJ]]
-[[Category: Sutcliffe, O B.]]
+[[Category: Sutcliffe OB]]
-[[Category: Thiyagarajan, N.]]
+[[Category: Thiyagarajan N]]
-[[Category: Woo, L W.L.]]
+[[Category: Woo LWL]]
-[[Category: Anti-cancer drug delivery]]
-[[Category: Carbonic anhydrase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:09:59 2008''