1cvb: Difference between revisions

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OCA

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-[[Image:1cvb.gif|left|200px]]<br />
-<applet load="1cvb" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1cvb, resolution 2.4&Aring;" />
-'''STRUCTURAL AND FUNCTIONAL IMPORTANCE OF A CONSERVED HYDROGEN BOND NETWORK IN HUMAN CARBONIC ANHYDRASE II'''<br />
-==Overview==
+==STRUCTURAL AND FUNCTIONAL IMPORTANCE OF A CONSERVED HYDROGEN BOND NETWORK IN HUMAN CARBONIC ANHYDRASE II==
-Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII), (Thr199--&gt;Ser, Ala, Val, and Pro) were characterized to investigate the, importance of a conserved hydrogen bonding network. The three-dimensional, structures of azide-bound and sulfate-bound T199V CAIIs were determined by, x-ray crystallographic methods at 2.25 and 2.4 A, respectively (final, crystallographic R factors are 0.173 and 0.174, respectively). The CO2, hydrase activities of T199S and T199P variants suggest that the side chain, methyl and backbone amino functionalities stabilize the transition state, by approximately 0.4 and 0.8 kcal/mol, respectively. The side chain, hydroxyl group causes: stabilization of zinc-hydroxide relative to, zinc-water (pKa increases approximately 2 units); stabilization of the, transition state for bicarbonate dehydration relative to the CAII.HCO3-, complex (approximately 5 kcal/mol); and destabilization of the CAII.HCO3-, complex (approximately 0.8 kcal/mol). An inverse correlation between, log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates, that the hydrogen bonding network stabilizes the chemical transition state, and zinc-hydroxide similarly. These data are consistent with the hydroxyl, group of Thr199 forming a hydrogen bond with the transition state and a, non-hydrogen-bonded van der Waals contact with CAII.HCO3-.
+<StructureSection load='1cvb' size='340' side='right'caption='[[1cvb]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1cvb]] 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=1CVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CVB 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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1cvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cvb OCA], [https://pdbe.org/1cvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cvb RCSB], [https://www.ebi.ac.uk/pdbsum/1cvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cvb 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/cv/1cvb_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=1cvb ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-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]]
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-CVB 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 ZN and SO4 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CVB OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural and functional importance of a conserved hydrogen bond network in human carbonic anhydrase II., Krebs JF, Ippolito JA, Christianson DW, Fierke CA, J Biol Chem. 1993 Dec 25;268(36):27458-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8262987 8262987]
-[[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson DW]]
-[[Category: Ippolito, J.A.]]
+[[Category: Ippolito JA]]
-[[Category: SO4]]
-[[Category: ZN]]
-[[Category: lyase(oxo-acid)]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:25:27 2007''