1z7x: Difference between revisions
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< | ==X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I== | ||
<StructureSection load='1z7x' size='340' side='right'caption='[[1z7x]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
You may | == 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]] 1.95Å</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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1z7x" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]] | |||
*[[Ribonuclease inhibitor|Ribonuclease inhibitor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
== | |||
< | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Allard | [[Category: Allard STM]] | ||
[[Category: Bingman | [[Category: Bingman CA]] | ||
[[Category: Bitto | [[Category: Bitto E]] | ||
[[Category: | [[Category: Johnson RJ]] | ||
[[Category: | [[Category: McCoy JG]] | ||
[[Category: Jr | [[Category: Phillips Jr GN]] | ||
[[Category: Raines RT]] | |||
[[Category: Raines | [[Category: Wesenberg GE]] | ||
[[Category: Wesenberg | |||
Latest revision as of 10:44, 30 October 2024
X-ray structure of human ribonuclease inhibitor complexed with ribonuclease IX-ray structure of human ribonuclease inhibitor complexed with ribonuclease I
Structural highlights
FunctionRNAS1_HUMAN Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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