1ttm: Difference between revisions

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-{{Seed}}
-[[Image:1ttm.png|left|200px]]
-<!--
+==Human carbonic anhydrase II complexed with 667-coumate==
-The line below this paragraph, containing "STRUCTURE_1ttm", creates the "Structure Box" on the page.
+<StructureSection load='1ttm' size='340' side='right'caption='[[1ttm]], [[Resolution|resolution]] 1.95&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'>[[1ttm]] 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=1TTM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TTM 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]] 1.95&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=667:6-OXO-8,9,10,11-TETRAHYDRO-7H-CYCLOHEPTA[C][1]BENZOPYRAN-3-O-SULFAMATE'>667</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_1ttm|  PDB=1ttm  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ttm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ttm OCA], [https://pdbe.org/1ttm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ttm RCSB], [https://www.ebi.ac.uk/pdbsum/1ttm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ttm 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/tt/1ttm_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=1ttm ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+CA (carbonic anhydrase) catalyses the reversible hydration of carbon dioxide into bicarbonate, and at least 14 isoforms have been identified in vertebrates. The role of CA type II in maintaining the fluid and pH balance has made it an attractive drug target for the treatment of glaucoma and cancer. 667-coumate is a potent inhibitor of the novel oncology target steroid sulphatase and is currently in Phase 1 clinical trials for hormone-dependent breast cancer. It also inhibits CA II in vitro. In the present study, CA II was crystallized with 667-coumate and the structure was determined by X-ray crystallography at 1.95 A (1 A=0.1 nm) resolution. The structure reported here is the first for an inhibitor based on a coumarin ring and shows ligation of the sulphamate group to the active-site zinc at 2.15 A through a nitrogen anion. The first two rings of the coumarin moiety are bound within the hydrophobic binding site of CA II. Important residues contributing to binding include Val-121, Phe-131, Val-135, Leu-141, Leu-198 and Pro-202. The third seven-membered ring is more mobile and is located in the channel leading to the surface of the enzyme. Pharmacokinetic studies show enhanced stability of 667-coumate in vivo and this has been ascribed to binding of CA II in erythrocytes. This result provides a structural basis for the stabilization and long half-life of 667-coumate in blood compared with its rapid disappearance in plasma, and suggests that reversible binding of inhibitors to CA may be a general method of delivering this type of labile drug.
-===Human carbonic anhydrase II complexed with 667-coumate===
+Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex with 667-coumate, a novel anti-cancer agent.,Lloyd MD, Pederick RL, Natesh R, Woo LW, Purohit A, Reed MJ, Acharya KR, Potter BV Biochem J. 2005 Feb 1;385(Pt 3):715-20. PMID:15453828<ref>PMID:15453828</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1ttm" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15453828}}, 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 15453828 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15453828}}
+__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==
-TTM is a 1 chain 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=1TTM OCA].
-==Reference==
-<ref group="xtra">PMID:15453828</ref><references group="xtra"/>
-[[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
-[[Category: Acharya, K R.]]
+[[Category: Large Structures]]
-[[Category: Lloyd, M D.]]
+[[Category: Acharya KR]]
-[[Category: Natesh, R.]]
+[[Category: Lloyd MD]]
-[[Category: Pederick, R L.]]
+[[Category: Natesh R]]
-[[Category: Potter, B V.L.]]
+[[Category: Pederick RL]]
-[[Category: Purohit, A.]]
+[[Category: Potter BVL]]
-[[Category: Reed, M J.]]
+[[Category: Purohit A]]
-[[Category: Woo, L W.L.]]
+[[Category: Reed MJ]]
-[[Category: 667-coumate]]
+[[Category: Woo LWL]]
-[[Category: Cancer]]
-[[Category: Human carbonic anhydrase inhibitor]]
-[[Category: Obesity]]
-[[Category: Steroid sulfatase inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 06:38:35 2009''