1z7x: Difference between revisions

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-[[Image:1z7x.gif|left|200px]]<br /><applet load="1z7x" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1z7x, resolution 1.95&Aring;" />
-'''X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I'''<br />
-==Overview==
+==X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I==
-The ribonuclease inhibitor protein (RI) binds to members of the bovine, pancreatic ribonuclease (RNase A) superfamily with an affinity in the, femtomolar range. Here, we report on structural and energetic aspects of, the interaction between human RI (hRI) and human pancreatic ribonuclease, (RNase 1). The structure of the crystalline hRI x RNase 1 complex was, determined at a resolution of 1.95 A, revealing the formation of 19, intermolecular hydrogen bonds involving 13 residues of RNase 1. In, contrast, only nine such hydrogen bonds are apparent in the structure of, the complex between porcine RI and RNase A. hRI, which is anionic, also, appears to use its horseshoe-shaped structure to engender long-range, Coulombic interactions with RNase 1, which is cationic. In accordance with, the structural data, the hRI.RNase 1 complex was found to be extremely, stable (t(1/2)=81 days; K(d)=2.9 x 10(-16) M). Site-directed mutagenesis, experiments enabled the identification of two cationic residues in RNase, 1, Arg39 and Arg91, that are especially important for both the formation, and stability of the complex, and are thus termed "electrostatic targeting, residues". Disturbing the electrostatic attraction between hRI and RNase 1, yielded a variant of RNase 1 that maintained ribonucleolytic activity and, conformational stability but had a 2.8 x 10(3)-fold lower association rate, for complex formation and 5.9 x 10(9)-fold lower affinity for hRI. This, variant of RNase 1, which exhibits the largest decrease in RI affinity of, any engineered ribonuclease, is also toxic to human erythroleukemia cells., Together, these results provide new insight into an unusual and important, protein-protein interaction, and could expedite the development of human, ribonucleases as chemotherapeutic agents.
+<StructureSection load='1z7x' size='340' side='right'caption='[[1z7x]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1z7x]] 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=1Z7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z7X 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]] 1.95&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</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=1z7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z7x OCA], [https://pdbe.org/1z7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z7x RCSB], [https://www.ebi.ac.uk/pdbsum/1z7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z7x ProSAT], [https://www.topsan.org/Proteins/CESG/1z7x TOPSAN]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/RNAS1_HUMAN RNAS1_HUMAN] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.<ref>PMID:17350650</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/z7/1z7x_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1z7x ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The ribonuclease inhibitor protein (RI) binds to members of the bovine pancreatic ribonuclease (RNase A) superfamily with an affinity in the femtomolar range. Here, we report on structural and energetic aspects of the interaction between human RI (hRI) and human pancreatic ribonuclease (RNase 1). The structure of the crystalline hRI x RNase 1 complex was determined at a resolution of 1.95 A, revealing the formation of 19 intermolecular hydrogen bonds involving 13 residues of RNase 1. In contrast, only nine such hydrogen bonds are apparent in the structure of the complex between porcine RI and RNase A. hRI, which is anionic, also appears to use its horseshoe-shaped structure to engender long-range Coulombic interactions with RNase 1, which is cationic. In accordance with the structural data, the hRI.RNase 1 complex was found to be extremely stable (t(1/2)=81 days; K(d)=2.9 x 10(-16) M). Site-directed mutagenesis experiments enabled the identification of two cationic residues in RNase 1, Arg39 and Arg91, that are especially important for both the formation and stability of the complex, and are thus termed "electrostatic targeting residues". Disturbing the electrostatic attraction between hRI and RNase 1 yielded a variant of RNase 1 that maintained ribonucleolytic activity and conformational stability but had a 2.8 x 10(3)-fold lower association rate for complex formation and 5.9 x 10(9)-fold lower affinity for hRI. This variant of RNase 1, which exhibits the largest decrease in RI affinity of any engineered ribonuclease, is also toxic to human erythroleukemia cells. Together, these results provide new insight into an unusual and important protein-protein interaction, and could expedite the development of human ribonucleases as chemotherapeutic agents.
-==Disease==
+Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein.,Johnson RJ, McCoy JG, Bingman CA, Phillips GN Jr, Raines RT J Mol Biol. 2007 Apr 27;368(2):434-49. Epub 2007 Feb 9. PMID:17350650<ref>PMID:17350650</ref>
-Known diseases associated with this structure: Aicardi-Goutieres syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606034 606034]], 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]], 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]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Z7X 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 <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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:Cit+Binding+Site+For+Residue+X+900'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7X OCA].
+</div>
+<div class="pdbe-citations 1z7x" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein., Johnson RJ, McCoy JG, Bingman CA, Phillips GN Jr, Raines RT, J Mol Biol. 2007 Apr 27;368(2):434-49. Epub 2007 Feb 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17350650 17350650]
+*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
+*[[Ribonuclease inhibitor|Ribonuclease inhibitor]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Pancreatic ribonuclease]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
+[[Category: Allard STM]]
-[[Category: Allard, S.T.M.]]
+[[Category: Bingman CA]]
-[[Category: Bingman, C.A.]]
+[[Category: Bitto E]]
-[[Category: Bitto, E.]]
+[[Category: Johnson RJ]]
-[[Category: CESG, Center.for.Eukaryotic.Structural.Genomics.]]
+[[Category: McCoy JG]]
-[[Category: Johnson, R.J.]]
+[[Category: Phillips Jr GN]]
-[[Category: Jr., G.N.Phillips.]]
+[[Category: Raines RT]]
-[[Category: McCoy, J.G.]]
+[[Category: Wesenberg GE]]
-[[Category: Raines, R.T.]]
-[[Category: Wesenberg, G.E.]]
-[[Category: CIT]]
-[[Category: center for eukaryotic structural genomics]]
-[[Category: cesg]]
-[[Category: enzyme-inhibitor complex]]
-[[Category: hydrolase/hydrolase inhibitor complex]]
-[[Category: leucine-rich repeat]]
-[[Category: protein structure initiative]]
-[[Category: psi]]
-[[Category: ribonuclease-inhibitor complex]]
-[[Category: structural genomics]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:16:47 2008''