2q1q: Difference between revisions

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-[[Image:2q1q.jpg|left|200px]]<br /><applet load="2q1q" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2q1q, resolution 1.90&Aring;" />
-'''Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies'''<br />
-==Overview==
+==Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: kinetic and X-Ray crystallographic studies==
-Sulthiame, a clinically used antiepileptic, was investigated for its, interaction with 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The drug is a potent inhibitor of CA II, VII, IX, and XII (K(I)s of 6-56nM), and a medium potency inhibitor against CA IV, VA, VB, and VI (K(I)s of 81-134nM). The high resolution crystal structure, of the hCA II-sulthiame adduct revealed a large number of favorable, interactions between the drug and the enzyme which explain its strong low, nanomolar affinity for this isoform and may also be exploited for the, design of effective inhibitors incorporating sultam moieties.
+<StructureSection load='2q1q' size='340' side='right'caption='[[2q1q]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2q1q]] 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=2Q1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q1Q 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]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=OSP:SULTHIAME'>OSP</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=2q1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1q OCA], [https://pdbe.org/2q1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q1q RCSB], [https://www.ebi.ac.uk/pdbsum/2q1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q1q 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/q1/2q1q_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=2q1q ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-Q1Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HG:'>HG</scene> and <scene name='pdbligand=OSP:'>OSP</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1Q OCA].
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Carbonic anhydrase inhibitors. Interaction of the antiepileptic drug sulthiame with twelve mammalian isoforms: Kinetic and X-ray crystallographic studies., Temperini C, Innocenti A, Mastrolorenzo A, Scozzafava A, Supuran CT, Bioorg Med Chem Lett. 2007 Sep 1;17(17):4866-72. Epub 2007 Jun 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17588751 17588751]
+__TOC__
-[[Category: Carbonate dehydratase]]
+</StructureSection>
-[[Category: Single protein]]
+[[Category: Homo sapiens]]
-[[Category: Innocenti, A.]]
+[[Category: Large Structures]]
-[[Category: Mastrolorenzo, A.]]
+[[Category: Innocenti A]]
-[[Category: Scozzafava, A.]]
+[[Category: Mastrolorenzo A]]
-[[Category: Supuran, C.T.]]
+[[Category: Scozzafava A]]
-[[Category: Temperini, C.]]
+[[Category: Supuran CT]]
-[[Category: HG]]
+[[Category: Temperini C]]
-[[Category: OSP]]
-[[Category: ZN]]
-[[Category: antiepileptic]]
-[[Category: carbonic anhydrase]]
-[[Category: crystal structure]]
-[[Category: inhibitors]]
-[[Category: lyase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:40:16 2008''