1z7x: Difference between revisions

Revision as of 17:17, 3 May 2008

X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I

OverviewOverview

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.

About this StructureAbout this Structure

1Z7X is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sat May 3 17:17:20 2008

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OCA

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 [[Image:1z7x.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1z7x |SIZE=350|CAPTION= <scene name='initialview01'>1z7x</scene>, resolution 1.95&Aring;
+The line below this paragraph, containing "STRUCTURE_1z7x", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Cit+Binding+Site+For+Residue+X+900'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= RNASE1, RIB1, RNS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RNH, PRI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00163 RNAse_Pc], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00116 LRR_RI]</span>
+{{STRUCTURE_1z7x|  PDB=1z7x  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z7x OCA], [http://www.ebi.ac.uk/pdbsum/1z7x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z7x RCSB]</span>
-}}
 '''X-ray structure of human ribonuclease inhibitor complexed with ribonuclease I'''
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 [[Category: Raines, R T.]]
 [[Category: Wesenberg, G E.]]
-[[Category: center for eukaryotic structural genomic]]
+[[Category: Center for eukaryotic structural genomic]]
-[[Category: cesg]]
+[[Category: Cesg]]
-[[Category: enzyme-inhibitor complex]]
+[[Category: Enzyme-inhibitor complex]]
-[[Category: hydrolase/hydrolase inhibitor complex]]
+[[Category: Hydrolase/hydrolase inhibitor complex]]
-[[Category: leucine-rich repeat]]
+[[Category: Leucine-rich repeat]]
-[[Category: protein structure initiative]]
+[[Category: Protein structure initiative]]
-[[Category: psi]]
+[[Category: Psi]]
-[[Category: ribonuclease-inhibitor complex]]
+[[Category: Ribonuclease-inhibitor complex]]
-[[Category: structural genomic]]
+[[Category: Structural genomic]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 17:17:20 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:31:30 2008''