1cvd: Difference between revisions

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-[[Image:1cvd.jpg|left|200px]]<br /><applet load="1cvd" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1cvd, resolution 2.2&Aring;" />
-'''STRUCTURAL CONSEQUENCES OF REDESIGNING A PROTEIN-ZINC BINDING SITE'''<br />
-==Overview==
+==STRUCTURAL CONSEQUENCES OF REDESIGNING A PROTEIN-ZINC BINDING SITE==
-In order to probe the structural importance of zinc ligands in the active, site of human carbonic anhydrase II (CAII), we have determined the, three-dimensional structures of H94C (in metal-bound form), H94C-BME, (i.e., disulfide-linked with beta-mercaptoethanol), H94A, H96C, H119C, and, H119D variants of CAII by X-ray crystallographic methods at resolutions of, 2.2, 2.35, 2.25, 2.3, 2.2, and 2.25 A, respectively. Each variant, crystallizes isomorphously with the wild-type enzyme, in which zinc is, tetrahedrally coordinated by H94, H96, H119, and hydroxide ion. The, structure of H94C CAII reveals the successful substitution of the, naturally occurring histidine zinc ligand by a cysteine thiolate, and, metal coordination by C94 is facilitated by the plastic structural, response of the beta-sheet superstructure. Importantly, the resulting, structure represents the catalytically active form of the enzyme reported, previously [Alexander, R. S., Kiefer, L. L., Fierke, C. A., &amp;, Christianson, D. W. (1993) Biochemistry 32, 1510-1518]. Contrastingly, the, structure of H96C CAII reveals that the engineered side chain does not, coordinate to zinc; instead, zinc is tetrahedrally liganded by H94, H119, and two solvent molecules. Thus, the beta-sheet superstructure is not, sufficiently plastic in this location to allow C96 to coordinate to the, metal ion. Substitution of the thiolate or carboxylate group for wild-type, histidine in H119C and H119D CAIIs reveals that tetrahedral metal, coordination is maintained in each variant; however, since there is no, plastic structural response of the corresponding beta-strand, a longer, metal-ligand separation results.(ABSTRACT TRUNCATED AT 250 WORDS)
+<StructureSection load='1cvd' size='340' side='right'caption='[[1cvd]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1cvd]] 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=1CVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CVD 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=1cvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cvd OCA], [https://pdbe.org/1cvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cvd RCSB], [https://www.ebi.ac.uk/pdbsum/1cvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cvd 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/1cvd_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=1cvd 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/>
-CVD 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 <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1CVD OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural consequences of redesigning a protein-zinc binding site., Ippolito JA, Christianson DW, Biochemistry. 1994 Dec 27;33(51):15241-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7803386 7803386]
-[[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: ZN]]
-[[Category: lyase(oxo-acid)]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:37:20 2008''