2q4g | pdb_00002q4g

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Ensemble refinement of the protein crystal structure of human ribonuclease inhibitor complexed with ribonuclease I

spinqualitylabelsall models 2q4g, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q4g is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CIT Related: 1z7x Gene: RNASE1, RIB1, RNS1 (HUMAN), RNH1, PRI, RNH (HUMAN) Activity: Pancreatic ribonuclease, with EC number 3.1.27.5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Warning: this is a large structure, and loading might take a long time or not happen at all. Function [RNAS1_HUMAN] Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA. [RINI_HUMAN] Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis. 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribonuclease Ribonuclease inhibitor Temp

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