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PDBsum entry 2bnh

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protein links
Acetylation PDB id
2bnh
Jmol
Contents
Protein chain
457 a.a. *
Waters ×64
* Residue conservation analysis
PDB id:
2bnh
Name: Acetylation
Title: Porcine ribonuclease inhibitor
Structure: Ribonuclease inhibitor. Chain: a. Synonym: rnase inhibitor, ribonuclease/angiogenin inhibitor
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: liver
Resolution:
2.30Å     R-factor:   0.200    
Authors: B.Kobe,J.Deisenhofer
Key ref:
B.Kobe and J.Deisenhofer (1996). Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A. J Mol Biol, 264, 1028-1043. PubMed id: 9000628 DOI: 10.1006/jmbi.1996.0694
Date:
29-Jun-96     Release date:   12-Mar-97    
Supersedes: 1bnh
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10775  (RINI_PIG) -  Ribonuclease inhibitor
Seq:
Struc:
456 a.a.
456 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 

 

 
DOI no: 10.1006/jmbi.1996.0694 J Mol Biol 264:1028-1043 (1996)
PubMed id: 9000628  
 
 
Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A.
B.Kobe, J.Deisenhofer.
 
  ABSTRACT  
 
We describe the mechanism of ribonuclease inhibition by ribonuclease inhibitor, a protein built of leucine-rich repeats, based on the crystal structure of the complex between the inhibitor and ribonuclease A. The structure was determined by molecular replacement and refined to an Rcryst of 19.4% at 2.5 A resolution. Ribonuclease A binds to the concave region of the inhibitor protein comprising its parallel beta-sheet and loops. The inhibitor covers the ribonuclease active site and directly contacts several active-site residues. The inhibitor only partially mimics the RNase-nucleotide interaction and does not utilize the p1 phosphate-binding pocket of ribonuclease A, where a sulfate ion remains bound. The 2550 A2 of accessible surface area buried upon complex formation may be one of the major contributors to the extremely tight association (Ki = 5.9 x 10(-14) M). The interaction is predominantly electrostatic; there is a high chemical complementarity with 18 putative hydrogen bonds and salt links, but the shape complementarity is lower than in most other protein-protein complexes. Ribonuclease inhibitor changes its conformation upon complex formation; the conformational change is unusual in that it is a plastic reorganization of the entire structure without any obvious hinge and reflects the conformational flexibility of the structure of the inhibitor. There is a good agreement between the crystal structure and other biochemical studies of the interaction. The structure suggests that the conformational flexibility of RI and an unusually large contact area that compensates for a lower degree of complementarity may be the principal reasons for the ability of RI to potently inhibit diverse ribonucleases. However, the inhibition is lost with amphibian ribonucleases that have substituted most residues corresponding to inhibitor-binding residues in RNase A, and with bovine seminal ribonuclease that prevents inhibitor binding by forming a dimer.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Conformational changes in RI. The models of RI from the RNase A-RI complex (continuous lines) and RI from the lithium sulfate crystals (broken lines) were superimposed on the high-resol- ution model of free RI with the program INSIGHT (using only the C a atoms). The r.m.s. deviations of the C a atoms are shown as thin lines, and the fourth-order poly- nomial curves fitted to the r.m.s. deviations curves are shown as thick lines.
Figure 4.
Figure 4. An annealed omit electron density in the active site of RNase A. An 8 Å sphere around the sulfate ion in the RNase active site was omitted and the immediate surrounding atoms consisting of a 3 Å shell were restrained to avoid artificial movement into the omitted region. Simulated annealing was run with a starting temperature of 1000 Å . The stereo view of the electron density calculated with the phases derived from the omitted model and coefficients =Fobs= - =Fcalc= for data between 40 and 2.5 Å , was contoured at 3s and plotted with a program written by D. Xia. Superimposed is the model of the RNase A-RI complex. RNase A residues are indicated with E, and RI residues are indicated with I.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 264, 1028-1043) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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Structure-cytotoxicity relationships in bovine seminal ribonuclease: new insights from heat and chemical denaturation studies on variants.
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21134128 U.Arnold, F.Leich, P.Neumann, H.Lilie, and R.Ulbrich-Hofmann (2011).
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PDB codes: 3mwq 3mwr 3mx8
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18518759 A.K.Beck, H.I.Pass, M.Carbone, and H.Yang (2008).
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17729269 A.May, and M.Zacharias (2008).
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18161747 D.Marks, and A.Segal (2008).
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17868092 G.R.Marshall, J.A.Feng, and D.J.Kuster (2008).
Back to the future: ribonuclease A.
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18979636 G.Torrent, A.Benito, J.Castro, M.Ribó, and M.Vilanova (2008).
Contribution of the C30/C75 disulfide bond to the biological properties of onconase.
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18930025 R.F.Turcotte, and R.T.Raines (2008).
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19025416 R.F.Turcotte, and R.T.Raines (2008).
Design and characterization of an HIV-specific ribonuclease zymogen.
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18673284 T.J.Rutkoski, and R.T.Raines (2008).
Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity.
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17283206 E.Andersen-Nissen, K.D.Smith, R.Bonneau, R.K.Strong, and A.Aderem (2007).
A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin.
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17786587 G.N.Phillips, B.G.Fox, J.L.Markley, B.F.Volkman, E.Bae, E.Bitto, C.A.Bingman, R.O.Frederick, J.G.McCoy, B.L.Lytle, B.S.Pierce, J.Song, and S.N.Twigger (2007).
Structures of proteins of biomedical interest from the Center for Eukaryotic Structural Genomics.
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17672523 L.D.Lavis, T.J.Rutkoski, and R.T.Raines (2007).
Tuning the pK(a) of fluorescein to optimize binding assays.
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17138564 M.Ghosh, G.Meiss, A.M.Pingoud, R.E.London, and L.C.Pedersen (2007).
The nuclease a-inhibitor complex is characterized by a novel metal ion bridge.
  J Biol Chem, 282, 5682-5690.
PDB code: 2o3b
17517123 N.Matsushima, T.Tanaka, P.Enkhbayar, T.Mikami, M.Taga, K.Yamada, and Y.Kuroki (2007).
Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors.
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17350650 R.J.Johnson, J.G.McCoy, C.A.Bingman, G.N.Phillips, and R.T.Raines (2007).
Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein.
  J Mol Biol, 368, 434-449.
PDB codes: 1z7x 2q4g
17956129 R.J.Johnson, L.D.Lavis, and R.T.Raines (2007).
Intraspecies regulation of ribonucleolytic activity.
  Biochemistry, 46, 13131-13140.  
17073304 B.Zhou, S.Qu, G.Liu, M.Dolan, H.Sakai, G.Lu, M.Bellizzi, and G.L.Wang (2006).
The eight amino-acid differences within three leucine-rich repeats between Pi2 and Piz-t resistance proteins determine the resistance specificity to Magnaporthe grisea.
  Mol Plant Microbe Interact, 19, 1216-1228.  
17032310 H.Yagi, M.Ueda, H.Jinno, K.Aiura, S.Mikami, H.Tada, M.Seno, H.Yamada, and M.Kitajima (2006).
Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties.
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16791850 L.M.Kallay, A.McNickle, P.J.Brennwald, A.L.Hubbard, and L.T.Braiterman (2006).
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16403589 S.Schornack, A.Meyer, P.Römer, T.Jordan, and T.Lahaye (2006).
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16551257 Z.Pancer, and M.D.Cooper (2006).
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16880994 A.Benito, M.Ribó, and M.Vilanova (2005).
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15572351 C.Korn, S.R.Scholz, O.Gimadutdinow, R.Lurz, A.Pingoud, and G.Meiss (2005).
Interaction of DNA fragmentation factor (DFF) with DNA reveals an unprecedented mechanism for nuclease inhibition and suggests that DFF can be activated in a DNA-bound state.
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15695505 E.E.Büllesbach, and C.Schwabe (2005).
The trap-like relaxin-binding site of the leucine-rich G-protein-coupled receptor 7.
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15961631 J.Choe, M.S.Kelker, and I.A.Wilson (2005).
Crystal structure of human toll-like receptor 3 (TLR3) ectodomain.
  Science, 309, 581-585.
PDB code: 1ziw
16164979 K.A.Dickson, M.C.Haigis, and R.T.Raines (2005).
Ribonuclease inhibitor: structure and function.
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16373579 M.N.Alder, I.B.Rogozin, L.M.Iyer, G.V.Glazko, M.D.Cooper, and Z.Pancer (2005).
Diversity and function of adaptive immune receptors in a jawless vertebrate.
  Science, 310, 1970-1973.  
15645301 Z.Wang, L.Zhang, J.Lu, and L.Zhang (2005).
Analysis of the interactions of ribonuclease inhibitor with kanamycin.
  J Mol Model, 11, 80-86.  
14681553 K.Kumar, M.Brady, and R.Shapiro (2004).
Selective abolition of pancreatic RNase binding to its inhibitor protein.
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15565466 M.G.Martínez Zamora, A.P.Castagnaro, and J.C.Díaz Ricci (2004).
Isolation and diversity analysis of resistance gene analogues (RGAs) from cultivated and wild strawberries.
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14760739 P.Forrer, H.K.Binz, M.T.Stumpp, and A.Plückthun (2004).
Consensus design of repeat proteins.
  Chembiochem, 5, 183-189.  
12709057 A.Bracale, F.Castaldi, L.Nitsch, and G.D'Alessio (2003).
A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action.
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12904578 A.Di Matteo, L.Federici, B.Mattei, G.Salvi, K.A.Johnson, C.Savino, G.De Lorenzo, D.Tsernoglou, and F.Cervone (2003).
The crystal structure of polygalacturonase-inhibiting protein (PGIP), a leucine-rich repeat protein involved in plant defense.
  Proc Natl Acad Sci U S A, 100, 10124-10128.
PDB code: 1ogq
12649287 B.D.Smith, M.B.Soellner, and R.T.Raines (2003).
Potent inhibition of ribonuclease A by oligo(vinylsulfonic acid).
  J Biol Chem, 278, 20934-20938.  
12495728 B.F.Holt, D.A.Hubert, and J.L.Dangl (2003).
Resistance gene signaling in plants--complex similarities to animal innate immunity.
  Curr Opin Immunol, 15, 20-25.  
12497602 D.B.Gordon, G.K.Hom, S.L.Mayo, and N.A.Pierce (2003).
Exact rotamer optimization for protein design.
  J Comput Chem, 24, 232-243.  
12601689 H.Wu, and S.M.King (2003).
Backbone dynamics of dynein light chains.
  Cell Motil Cytoskeleton, 54, 267-273.  
14552836 J.K.Bell, G.E.Mullen, C.A.Leifer, A.Mazzoni, D.R.Davies, and D.M.Segal (2003).
Leucine-rich repeats and pathogen recognition in Toll-like receptors.
  Trends Immunol, 24, 528-533.  
12697760 J.Matousek, G.Gotte, P.Pouckova, J.Soucek, T.Slavik, F.Vottariello, and M.Libonati (2003).
Antitumor activity and other biological actions of oligomers of ribonuclease A.
  J Biol Chem, 278, 23817-23822.  
12560499 M.C.Haigis, E.L.Kurten, and R.T.Raines (2003).
Ribonuclease inhibitor as an intracellular sentry.
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12377788 A.Russo, A.Antignani, C.Giancola, and G.D'Alessio (2002).
Engineering the refolding pathway and the quaternary structure of seminal ribonuclease by newly introduced disulfide bridges.
  J Biol Chem, 277, 48643-48649.  
12106974 J.Matousek, P.Poucková, J.Soucek, and J.Skvor (2002).
PEG chains increase aspermatogenic and antitumor activity of RNase A and BS-RNase enzymes.
  J Control Release, 82, 29-37.  
12105206 M.Santra, C.C.Reed, and R.V.Iozzo (2002).
Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope.
  J Biol Chem, 277, 35671-35681.  
  18628868 B.Mattei, F.Cervone, and P.Roepstorff (2001).
The Interaction Between Endopolygalacturonase From Fusarium Moniliforme and PGIP from Phaseolus Vulgaris Studied by Surface Plasmon Resonance and Mass Spectrometry.
  Comp Funct Genomics, 2, 359-364.  
11555655 P.A.Leland, K.E.Staniszewski, B.M.Kim, and R.T.Raines (2001).
Endowing human pancreatic ribonuclease with toxicity for cancer cells.
  J Biol Chem, 276, 43095-43102.  
11358688 P.A.Leland, and R.T.Raines (2001).
Cancer chemotherapy--ribonucleases to the rescue.
  Chem Biol, 8, 405-413.  
11259599 Y.G.Hsiung, H.C.Chang, J.L.Pellequer, R.La Valle, S.Lanker, and C.Wittenberg (2001).
F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat.
  Mol Cell Biol, 21, 2506-2520.  
10744660 L.E.Bretscher, R.L.Abel, and R.T.Raines (2000).
A ribonuclease A variant with low catalytic activity but high cytotoxicity.
  J Biol Chem, 275, 9893-9896.  
10656267 N.Matsushima, T.Ohyanagi, T.Tanaka, and R.H.Kretsinger (2000).
Super-motifs and evolution of tandem leucine-rich repeats within the small proteoglycans--biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, osteoadherin, epiphycan, and osteoglycin.
  Proteins, 38, 210-225.  
10413501 C.Z.Chen, and R.Shapiro (1999).
Superadditive and subadditive effects of "hot spot" mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A.
  Biochemistry, 38, 9273-9285.  
10228150 F.Leckie, B.Mattei, C.Capodicasa, A.Hemmings, L.Nuss, B.Aracri, G.De Lorenzo, and F.Cervone (1999).
The specificity of polygalacturonase-inhibiting protein (PGIP): a single amino acid substitution in the solvent-exposed beta-strand/beta-turn region of the leucine-rich repeats (LRRs) confers a new recognition capability.
  EMBO J, 18, 2352-2363.  
9724716 P.A.Leland, L.W.Schultz, B.M.Kim, and R.T.Raines (1998).
Ribonuclease A variants with potent cytotoxic activity.
  Proc Natl Acad Sci U S A, 95, 10407-10412.  
9311977 A.C.Papageorgiou, R.Shapiro, and K.R.Acharya (1997).
Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution.
  EMBO J, 16, 5162-5177.
PDB code: 1a4y
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