1yda: Difference between revisions

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-[[Image:1yda.gif|left|200px]]<br />
-<applet load="1yda" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1yda, resolution 2.1&Aring;" />
-'''STRUCTURAL BASIS OF INHIBITOR AFFINITY TO VARIANTS OF HUMAN CARBONIC ANHYDRASE II'''<br />
-==Overview==
+==STRUCTURAL BASIS OF INHIBITOR AFFINITY TO VARIANTS OF HUMAN CARBONIC ANHYDRASE II==
-The activities and structures of certain L198 variants of human carbonic, anhydrase II (CAII) have been reported recently [Krebs, J. F., Rana, F., Dluhy, R. A., &amp; Fierke, C. A. (1993) Biochemistry 32, 4496-4505; Nair, S., K., &amp; Christianson, D. W. (1993) Biochemistry 32, 4506-4514]. In order to, understand the structural basis of enzyme-inhibitor affinity, we now, report the dissociation rate and equilibrium constants for acetazolamide, and dansylamide binding to 13 variants of CAII containing substituted, amino acids at position 198. These data indicate that inhibitor affinity, is modulated by the hydrophobicity and charge of the 198 side chain., Furthermore, we have determined crystal structures of L198R, L198E, and, L198F CAIIs complexed with the transition state analog acetazolamide. The, substituted benzyl side chain of L198F CAII does not occlude the substrate, association pocket, and it is therefore not surprising that this, substitution has minimal effects on catalytic properties and inhibitor, binding. Nevertheless, the F198 side chain undergoes a significant, conformation change in order to accommodate the binding of acetazolamide;, the same behavior is observed for the engineered side chain of L198R CAII., In contrast, the engineered side chain of L198E CAII does not alter its, conformation upon inhibitor binding. We conclude that the mobility and, hydrophobicity or residue 198 side chains affect enzyme-inhibitor (and, enzyme-substrate) affinity, and these structure-function relationships are, important for understanding the behavior of carbonic anhydrase isozyme, III, which bears a wild-type F198 side chain.(ABSTRACT TRUNCATED AT 250, WORDS)
+<StructureSection load='1yda' size='340' side='right'caption='[[1yda]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1yda]] 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=1YDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YDA 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]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZM:5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE'>AZM</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=1yda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yda OCA], [https://pdbe.org/1yda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yda RCSB], [https://www.ebi.ac.uk/pdbsum/1yda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yda 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/yd/1yda_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=1yda 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/>
-YDA 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, HG and AZM 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=1YDA OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural basis of inhibitor affinity to variants of human carbonic anhydrase II., Nair SK, Krebs JF, Christianson DW, Fierke CA, Biochemistry. 1995 Mar 28;34(12):3981-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7696263 7696263]
-[[Category: Carbonate dehydratase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson DW]]
-[[Category: Nair, S.K.]]
+[[Category: Nair SK]]
-[[Category: AZM]]
-[[Category: HG]]
-[[Category: ZN]]
-[[Category: hydro-lyase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:18:13 2007''