1a42: Difference between revisions

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-[[Image:1a42.gif|left|200px]]<br />
-<applet load="1a42" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1a42, resolution 2.25&Aring;" />
-'''HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH BRINZOLAMIDE'''<br />
-==Overview==
+==HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH BRINZOLAMIDE==
-Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to, plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have, determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV. We have also determined the, structure of its complex with a drug used for glaucoma therapy, the, sulfonamide inhibitor brinzolamide (Azopt). The overall structure of, murine CAIV is generally similar to that of human CAIV; however, some, local structural differences are found in the active site resulting from, amino acid sequence differences in the "130's segment" and the residue-63, loop (these may affect the nearby catalytic proton shuttle, His-64)., Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a, ... [[http://ispc.weizmann.ac.il/pmbin/getpm?9541386 (full description)]]
+<StructureSection load='1a42' size='340' side='right'caption='[[1a42]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1a42]] 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=1A42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A42 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]] 2.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BZU:(4R)-2-(2-ETHOXYETHYL)-4-(ETHYLAMINO)-3,4-DIHYDRO-2H-THIENO[3,2-E][1,2]THIAZINE-6-SULFONAMIDE+1,1-DIOXIDE'>BZU</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=1a42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a42 OCA], [https://pdbe.org/1a42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a42 RCSB], [https://www.ebi.ac.uk/pdbsum/1a42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a42 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/a4/1a42_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=1a42 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-A42 is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with HG, ZN and BZU as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[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]]. Structure known Active Site: ZN. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A42 OCA]].
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination., Stams T, Chen Y, Boriack-Sjodin PA, Hurt JD, Liao J, May JA, Dean T, Laipis P, Silverman DN, Christianson DW, Protein Sci. 1998 Mar;7(3):556-63. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9541386 9541386]
+__TOC__
-[[Category: Carbonate dehydratase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Boriack-Sjodin, P.A.]]
+[[Category: Boriack-Sjodin PA]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson DW]]
-[[Category: BZU]]
-[[Category: HG]]
-[[Category: ZN]]
-[[Category: inhibitor]]
-[[Category: lyase]]
-[[Category: zinc]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 14:44:40 2007''