2bex

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[[Image:2bex.gif|left|200px]]<br /><applet load="2bex" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2bex, resolution 1.99&Aring;" />
 
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'''CRYSTAL STRUCTURE OF PLACENTAL RIBONUCLEASE INHIBITOR IN COMPLEX WITH HUMAN EOSINOPHIL DERIVED NEUROTOXIN AT 2A RESOLUTION'''<br />
 
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==Overview==
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==Crystal structure of Placental Ribonuclease Inhibitor in complex with Human Eosinophil Derived Neurotoxin at 2A resolution==
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Placental ribonuclease inhibitor (RI) binds diverse mammalian RNases with, dissociation constants that are in the femtomolar range. Previous studies, on the complexes of RI with RNase A and angiogenin revealed that RI, utilises largely distinctive interactions to achieve high affinity for, these two ligands. Here we report a 2.0 angstroms resolution crystal, structure of RI in complex with a third ligand, eosinophil-derived, neurotoxin (EDN), and a mutational analysis based on this structure. The, RI-EDN interface is more extensive than those of the other two complexes, and contains a considerably larger set of interactions. Few of the, contacts present in the RI-angiogenin complex are replicated; the, correspondence to the RI-RNase A complex is somewhat greater, but still, modest. The energetic contributions of various interface regions differ, strikingly from those in the earlier complexes. These findings provide, insight into the structural basis for the unusual combination of high, avidity and relaxed stringency that RI displays.
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<StructureSection load='2bex' size='340' side='right'caption='[[2bex]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2bex]] is a 4 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=2BEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BEX FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAK:ALPHA-KETOMALONIC+ACID'>MAK</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bex OCA], [https://pdbe.org/2bex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bex RCSB], [https://www.ebi.ac.uk/pdbsum/2bex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bex ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RINI_HUMAN RINI_HUMAN] Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis.<ref>PMID:14515218</ref> <ref>PMID:12578357</ref> <ref>PMID:17292889</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/be/2bex_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2bex ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Placental ribonuclease inhibitor (RI) binds diverse mammalian RNases with dissociation constants that are in the femtomolar range. Previous studies on the complexes of RI with RNase A and angiogenin revealed that RI utilises largely distinctive interactions to achieve high affinity for these two ligands. Here we report a 2.0 angstroms resolution crystal structure of RI in complex with a third ligand, eosinophil-derived neurotoxin (EDN), and a mutational analysis based on this structure. The RI-EDN interface is more extensive than those of the other two complexes and contains a considerably larger set of interactions. Few of the contacts present in the RI-angiogenin complex are replicated; the correspondence to the RI-RNase A complex is somewhat greater, but still modest. The energetic contributions of various interface regions differ strikingly from those in the earlier complexes. These findings provide insight into the structural basis for the unusual combination of high avidity and relaxed stringency that RI displays.
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==Disease==
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Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor.,Iyer S, Holloway DE, Kumar K, Shapiro R, Acharya KR J Mol Biol. 2005 Apr 1;347(3):637-55. PMID:15755456<ref>PMID:15755456</ref>
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Known diseases associated with this structure: Aicardi-Goutieres syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606034 606034]], Central hypoventilation syndrome, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]], Creutzfeldt-Jakob disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Gerstmann-Straussler disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Hirschsprung disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]], Huntington disease-like 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Insomnia, fatal familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Prion disease with protracted course OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Shah-Waardenburg syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131242 131242]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2BEX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MAK and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pancreatic_ribonuclease Pancreatic ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.27.5 3.1.27.5] Known structural/functional Site: <scene name='pdbsite=AC1:Mak Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BEX OCA].
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</div>
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<div class="pdbe-citations 2bex" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor., Iyer S, Holloway DE, Kumar K, Shapiro R, Acharya KR, J Mol Biol. 2005 Apr 1;347(3):637-55. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15755456 15755456]
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*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
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*[[Ribonuclease inhibitor|Ribonuclease inhibitor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Pancreatic ribonuclease]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Acharya KR]]
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[[Category: Acharya, K.R.]]
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[[Category: Holloway DE]]
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[[Category: Holloway, D.E.]]
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[[Category: Iyer S]]
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[[Category: Iyer, S.]]
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[[Category: Kumar K]]
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[[Category: Kumar, K.]]
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[[Category: Shapiro R]]
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[[Category: Shapiro, R.]]
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[[Category: GOL]]
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[[Category: MAK]]
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[[Category: eosinophil derived neurotoxin]]
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[[Category: luecine-rich repeats]]
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[[Category: molecular recognition]]
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[[Category: protein-protein interaction]]
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[[Category: ribonuclease inhibitor]]
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[[Category: rnase 2]]
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[[Category: x-ray crystallography]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:44:32 2007''
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Current revision

Crystal structure of Placental Ribonuclease Inhibitor in complex with Human Eosinophil Derived Neurotoxin at 2A resolution

PDB ID 2bex

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