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: | |
| 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.[1] [RINI_HUMAN] Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis.[2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Johnson RJ, McCoy JG, Bingman CA, Phillips GN Jr, Raines RT. Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. J Mol Biol. 2007 Apr 27;368(2):434-49. Epub 2007 Feb 9. PMID:17350650 doi:10.1016/j.jmb.2007.02.005
- ↑ Huang GH, Yang GZ, Chen JY, Wu XF. [Expression of a human ribonuclease inhibitor variant in Escherichia coli and silkworm insect cell (Bombyx mori)]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003 Oct;35(10):960-3. PMID:14515218
- ↑ Teufel DP, Kao RY, Acharya KR, Shapiro R. Mutational analysis of the complex of human RNase inhibitor and human eosinophil-derived neurotoxin (RNase 2). Biochemistry. 2003 Feb 18;42(6):1451-9. PMID:12578357 doi:10.1021/bi026852o
- ↑ Monti DM, Montesano Gesualdi N, Matousek J, Esposito F, D'Alessio G. The cytosolic ribonuclease inhibitor contributes to intracellular redox homeostasis. FEBS Lett. 2007 Mar 6;581(5):930-4. Epub 2007 Feb 6. PMID:17292889 doi:10.1016/j.febslet.2007.01.072
- ↑ Johnson RJ, McCoy JG, Bingman CA, Phillips GN Jr, Raines RT. Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. J Mol Biol. 2007 Apr 27;368(2):434-49. Epub 2007 Feb 9. PMID:17350650 doi:10.1016/j.jmb.2007.02.005
