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PDBsum entry 1rph

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Hydrolase(phosphoric diester) PDB id
1rph
Jmol
Contents
Protein chain
124 a.a. *
Ligands
SO4
Waters ×99
* Residue conservation analysis
PDB id:
1rph
Name: Hydrolase(phosphoric diester)
Title: Structures of rnase a complexed with 3'-cmp and d(cpa): active site conformation and conserved water molecules
Structure: Ribonuclease a. Chain: a. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Cell_line: s2. Organ: pancreas
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.158    
Authors: I.Zegers,L.Wyns,R.Palmer
Key ref:
I.Zegers et al. (1994). The structures of RNase A complexed with 3'-CMP and d(CpA): active site conformation and conserved water molecules. Protein Sci, 3, 2322-2339. PubMed id: 7756988 DOI: 10.1002/pro.5560031217
Date:
29-Aug-94     Release date:   20-Dec-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic
Seq:
Struc:
150 a.a.
124 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.27.5  - Pancreatic ribonuclease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     nucleic acid binding     7 terms  

 

 
DOI no: 10.1002/pro.5560031217 Protein Sci 3:2322-2339 (1994)
PubMed id: 7756988  
 
 
The structures of RNase A complexed with 3'-CMP and d(CpA): active site conformation and conserved water molecules.
I.Zegers, D.Maes, M.H.Dao-Thi, F.Poortmans, R.Palmer, L.Wyns.
 
  ABSTRACT  
 
The interactions of RNase A with cytidine 3'-monophosphate (3'-CMP) and deoxycytidyl-3',5'-deoxyadenosine (d(CpA)) were analyzed by X-ray crystallography. The 3'-CMP complex and the native structure were determined from trigonal crystals, and the d(CpA) complex from monoclinic crystals. The differences between the overall structures are concentrated in loop regions and are relatively small. The protein-inhibitor contacts are interpreted in terms of the catalytic mechanism. The general base His 12 interacts with the 2' oxygen, as does the electrostatic catalyst Lys 41. The general acid His 119 has 2 conformations (A and B) in the native structure and is found in, respectively, the A and the B conformation in the d(CpA) and the 3'-CMP complex. From the present structures and from a comparison with RNase T1, we propose that His 119 is active in the A conformation. The structure of the d(CpA) complex permits a detailed analysis of the downstream binding site, which includes His 119 and Asn 71. The comparison of the present RNase A structures with an inhibitor complex of RNase T1 shows that there are important similarities in the active sites of these 2 enzymes, despite the absence of any sequence homology. The water molecules were analyzed in order to identify conserved water sites. Seventeen water sites were found to be conserved in RNase A structures from 5 different space groups. It is proposed that 7 of those water molecules play a role in the binding of the N-terminal helix to the rest of the protein and in the stabilization of the active site.
 
  Selected figure(s)  
 
Figure 2.
IRPF P3221 2.2 116 15.5 pH 6, (NH4)2S04, NaCl 4SRN P3221 2.0 105 20.4 pH5.2,(NH4)2S04, CSCI
Figure 4.
RPF 4SRN
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1994, 3, 2322-2339) copyright 1994.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21205197 N.Thiyagarajan, B.D.Smith, R.T.Raines, and K.R.Acharya (2011).
Functional and structural analyses of N-acylsulfonamide-linked dinucleoside inhibitors of RNase A.
  FEBS J, 278, 541-549.
PDB codes: 2xog 2xoi
19191310 D.E.Holloway, G.B.Chavali, D.D.Leonidas, M.D.Baker, and K.R.Acharya (2009).
Influence of naturally-occurring 5'-pyrophosphate-linked substituents on the binding of adenylic inhibitors to ribonuclease a: An X-ray crystallographic study.
  Biopolymers, 91, 995.
PDB codes: 2w5g 2w5i 2w5k 2w5l 2w5m
19588901 N.Doucet, E.D.Watt, and J.P.Loria (2009).
The flexibility of a distant loop modulates active site motion and product release in ribonuclease A.
  Biochemistry, 48, 7160-7168.  
18508078 K.Kazakou, D.E.Holloway, S.H.Prior, V.Subramanian, and K.R.Acharya (2008).
Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications.
  J Mol Biol, 380, 206-222.
PDB codes: 2vq8 2vq9
17957392 S.A.Gabel, and R.E.London (2008).
Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry.
  J Biol Inorg Chem, 13, 207-217.  
17615241 E.D.Watt, H.Shimada, E.L.Kovrigin, and J.P.Loria (2007).
The mechanism of rate-limiting motions in enzyme function.
  Proc Natl Acad Sci U S A, 104, 11981-11986.  
18158891 N.G.Walter (2007).
Ribozyme catalysis revisited: is water involved?
  Mol Cell, 28, 923-929.  
  17768339 S.B.Larson, J.S.Day, R.Cudney, and A.McPherson (2007).
A new crystal form of bovine pancreatic RNase A in complex with 2'-deoxyguanosine-5'-monophosphate.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 728-733.
PDB code: 2qca
17142283 S.Polydoridis, D.D.Leonidas, N.G.Oikonomakos, and G.Archontis (2007).
Recognition of ribonuclease a by 3'-5'-pyrophosphate-linked dinucleotide inhibitors: a molecular dynamics/continuum electrostatics analysis.
  Biophys J, 92, 1659-1672.  
17397537 S.V.Rakhmanov, and V.J.Makeev (2007).
Atomic hydration potentials using a Monte Carlo Reference State (MCRS) for protein solvation modeling.
  BMC Struct Biol, 7, 19.  
16730994 D.D.Leonidas, T.K.Maiti, A.Samanta, S.Dasgupta, T.Pathak, S.E.Zographos, and N.G.Oikonomakos (2006).
The binding of 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine to ribonuclease A in the crystal.
  Bioorg Med Chem, 14, 6055-6064.
PDB codes: 2g8q 2g8r
16895992 F.Renzi, E.Caffarelli, P.Laneve, I.Bozzoni, M.Brunori, and B.Vallone (2006).
The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication.
  Proc Natl Acad Sci U S A, 103, 12365-12370.
PDB code: 2c1w
16301790 D.E.Holloway, G.B.Chavali, M.C.Hares, V.Subramanian, and K.R.Acharya (2005).
Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies.
  Acta Crystallogr D Biol Crystallogr, 61, 1568-1578.
PDB codes: 2bwk 2bwl
16045769 G.N.Hatzopoulos, D.D.Leonidas, R.Kardakaris, J.Kobe, and N.G.Oikonomakos (2005).
The binding of IMP to ribonuclease A.
  FEBS J, 272, 3988-4001.
PDB codes: 1z6d 1z6s
15048772 A.Merlino, L.Vitagliano, F.Sica, A.Zagari, and L.Mazzarella (2004).
Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer.
  Biopolymers, 73, 689-695.
PDB codes: 1r5c 1r5d
15041676 A.Merlino, L.Vitagliano, M.A.Ceruso, and L.Mazzarella (2004).
Dynamic properties of the N-terminal swapped dimer of ribonuclease A.
  Biophys J, 86, 2383-2391.  
15273275 N.G.Beloglazova, M.M.Fabani, M.A.Zenkova, E.V.Bichenkova, N.N.Polushin, V.V.Sil'nikov, K.T.Douglas, and V.V.Vlassov (2004).
Sequence-specific artificial ribonucleases. I. Bis-imidazole-containing oligonucleotide conjugates prepared using precursor-based strategy.
  Nucleic Acids Res, 32, 3887-3897.  
14704352 S.Fouace, C.Gaudin, S.Picard, S.Corvaisier, J.Renault, B.Carboni, and B.Felden (2004).
Polyamine derivatives as selective RNaseA mimics.
  Nucleic Acids Res, 32, 151-157.  
12833549 F.Sica, A.Di Fiore, A.Zagari, and L.Mazzarella (2003).
The unswapped chain of bovine seminal ribonuclease: Crystal structure of the free and liganded monomeric derivative.
  Proteins, 52, 263-271.
PDB codes: 1n1x 1n3z
12382288 A.Merlino, L.Vitagliano, M.A.Ceruso, A.Di Nola, and L.Mazzarella (2002).
Global and local motions in ribonuclease A: a molecular dynamics study.
  Biopolymers, 65, 274-283.  
12356310 C.G.Mohan, E.Boix, H.R.Evans, Z.Nikolovski, M.V.Nogués, C.M.Cuchillo, and K.R.Acharya (2002).
The crystal structure of eosinophil cationic protein in complex with 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic active site.
  Biochemistry, 41, 12100-12106.
PDB code: 1h1h
11742124 E.Chatani, R.Hayashi, H.Moriyama, and T.Ueki (2002).
Conformational strictness required for maximum activity and stability of bovine pancreatic ribonuclease A as revealed by crystallographic study of three Phe120 mutants at 1.4 A resolution.
  Protein Sci, 11, 72-81.
PDB codes: 1eic 1eid 1eie 1fs3
11746706 L.Vitagliano, A.Merlino, A.Zagari, and L.Mazzarella (2002).
Reversible substrate-induced domain motions in ribonuclease A.
  Proteins, 46, 97.
PDB codes: 1jvt 1jvu 1jvv
16233267 N.Tanimizu, H.Ueno, and R.Hayashi (2002).
Replacement of His12 or His119 of bovine pancreatic ribonuclease A with acidic amino acid residues for the modification of activity and stability.
  J Biosci Bioeng, 94, 39-44.  
12211010 S.P.Edgcomb, and K.P.Murphy (2002).
Variability in the pKa of histidine side-chains correlates with burial within proteins.
  Proteins, 49, 1-6.  
11264578 J.Pous, G.Mallorquí-Fernández, R.Peracaula, S.S.Terzyan, J.Futami, H.Tada, H.Yamada, M.Seno, R.de Llorens, F.X.Gomis-Rüth, and M.Coll (2001).
Three-dimensional structure of human RNase 1 delta N7 at 1.9 A resolution.
  Acta Crystallogr D Biol Crystallogr, 57, 498-505.
PDB code: 1e21
11093266 M.S.Madhusudhan, and S.Vishveshwara (2001).
Computer modeling of human angiogenin-dinucleotide substrate interaction.
  Proteins, 42, 125-135.  
11331006 R.J.Kubiak, X.Yue, R.J.Hondal, C.Mihai, M.D.Tsai, and K.S.Bruzik (2001).
Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond.
  Biochemistry, 40, 5422-5432.  
11530931 T.Greiner-Stöffele, H.H.Förster, H.J.Hofmann, and U.Hahn (2001).
RNase-stable RNA: conformational parameters of the nucleic acid backbone for binding to RNase T1.
  Biol Chem, 382, 1007-1017.  
11087402 B.R.Kelemen, L.W.Schultz, R.Y.Sweeney, and R.T.Raines (2000).
Excavating an active site: the nucleobase specificity of ribonuclease A.
  Biochemistry, 39, 14487-14494.
PDB code: 1c8w
  10892814 L.Vitagliano, A.Merlino, A.Zagari, and L.Mazzarella (2000).
Productive and nonproductive binding to ribonuclease A: X-ray structure of two complexes with uridylyl(2',5')guanosine.
  Protein Sci, 9, 1217-1225.
PDB codes: 1eos 1eow
  11206080 S.Orrù, L.Vitagliano, L.Esposito, L.Mazzarella, G.Marino, and M.Ruoppolo (2000).
Effect of deamidation on folding of ribonuclease A.
  Protein Sci, 9, 2577-2582.  
10547525 A.Peeters, and C.Van Alsenoy (1999).
Ab initio study of the reaction mechanism of ribonuclease A with cytidyl-3',5'-adenosine. I. Geometry optimization of cytidyl-3', 5'-adenosine.
  Biopolymers, 50, 697-704.  
10070263 M.S.Madhusudhan, and S.Vishveshwara (1999).
Comparison of the dynamics of bovine and human angiogenin: a molecular dynamics study.
  Biopolymers, 49, 131-144.  
10029539 R.K.Arni, L.Watanabe, R.J.Ward, R.J.Kreitman, K.Kumar, and F.G.Walz (1999).
Three-dimensional structure of ribonuclease T1 complexed with an isosteric phosphonate substrate analogue of GpU: alternate substrate binding modes and catalysis.
  Biochemistry, 38, 2452-2461.
PDB code: 1b2m
10373011 R.Loris, U.Langhorst, S.De Vos, K.Decanniere, J.Bouckaert, D.Maes, T.R.Transue, and J.Steyaert (1999).
Conserved water molecules in a large family of microbial ribonucleases.
  Proteins, 36, 117-134.
PDB codes: 1bu4 2bu4 3bu4 4bu4 5bu4
10194301 S.J.Evans, E.J.Shipstone, W.N.Maughan, and B.A.Connolly (1999).
Site-directed mutagenesis of phosphate-contacting amino acids of bovine pancreatic deoxyribonuclease I.
  Biochemistry, 38, 3902-3909.  
9860854 B.M.Fisher, L.W.Schultz, and R.T.Raines (1998).
Coulombic effects of remote subsites on the active site of ribonuclease A.
  Biochemistry, 37, 17386-17401.
PDB codes: 3rsk 4rsk
10089510 C.Sadasivan, H.G.Nagendra, and M.Vijayan (1998).
Plasticity, hydration and accessibility in ribonuclease A. The structure of a new crystal form and its low-humidity variant.
  Acta Crystallogr D Biol Crystallogr, 54, 1343-1352.
PDB codes: 1xps 1xpt
9521772 J.Wu, J.M.Adomat, T.W.Ridky, J.M.Louis, J.Leis, R.W.Harrison, and I.T.Weber (1998).
Structural basis for specificity of retroviral proteases.
  Biochemistry, 37, 4518-4526.
PDB codes: 1a94 1bai
  10082366 L.Vitagliano, S.Adinolfi, A.Riccio, F.Sica, A.Zagari, and L.Mazzarella (1998).
Binding of a substrate analog to a domain swapping protein: X-ray structure of the complex of bovine seminal ribonuclease with uridylyl(2',5')adenosine.
  Protein Sci, 7, 1691-1699.
PDB code: 11ba
9636030 L.W.Schultz, D.J.Quirk, and R.T.Raines (1998).
His...Asp catalytic dyad of ribonuclease A: structure and function of the wild-type, D121N, and D121A enzymes.
  Biochemistry, 37, 8886-8898.
PDB codes: 3rsd 4rsd
  9684895 L.W.Schultz, S.R.Hargraves, T.A.Klink, and R.T.Raines (1998).
Structure and stability of the P93G variant of ribonuclease A.
  Protein Sci, 7, 1620-1625.
PDB code: 3rsp
9578571 R.Shapiro (1998).
Structural features that determine the enzymatic potency and specificity of human angiogenin: threonine-80 and residues 58-70 and 116-123.
  Biochemistry, 37, 6847-6856.  
9435218 S.Shaltiel, S.Cox, and S.S.Taylor (1998).
Conserved water molecules contribute to the extensive network of interactions at the active site of protein kinase A.
  Proc Natl Acad Sci U S A, 95, 484-491.  
9649343 V.P.Denisov, and B.Halle (1998).
Thermal denaturation of ribonuclease A characterized by water 17O and 2H magnetic relaxation dispersion.
  Biochemistry, 37, 9595-9604.  
9370363 I.T.Weber, J.Wu, J.Adomat, R.W.Harrison, A.R.Kimmel, E.M.Wondrak, and J.M.Louis (1997).
Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates.
  Eur J Biochem, 249, 523-530.
PDB code: 1a8k
  9385639 I.T.Weber, and R.W.Harrison (1997).
Molecular mechanics calculations on Rous sarcoma virus protease with peptide substrates.
  Protein Sci, 6, 2365-2374.  
9249002 J.Steyaert (1997).
A decade of protein engineering on ribonuclease T1--atomic dissection of the enzyme-substrate interactions.
  Eur J Biochem, 247, 1.  
9461294 O.Lequin, H.Thüring, M.Robin, and J.Y.Lallemand (1997).
Three-dimensional solution structure of human angiogenin determined by 1H,15N-NMR spectroscopy--characterization of histidine protonation states and pKa values.
  Eur J Biochem, 250, 712-726.
PDB code: 1awz
9275172 R.Balakrishnan, N.Ramasubbu, K.I.Varughese, and R.Parthasarathy (1997).
Crystal structures of the copper and nickel complexes of RNase A: metal-induced interprotein interactions and identification of a novel copper binding motif.
  Proc Natl Acad Sci U S A, 94, 9620-9625.
PDB code: 1aqp
9135159 S.Y.Hsieh, T.P.Ko, M.Y.Tseng, W.Ku, K.F.Chak, and H.S.Yuan (1997).
A novel role of ImmE7 in the autoregulatory expression of the ColE7 operon and identification of possible RNase active sites in the crystal structure of dimeric ImmE7.
  EMBO J, 16, 1444-1454.
PDB code: 1unk
  8844852 C.Toiron, C.González, M.Bruix, and M.Rico (1996).
Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',5'-d(CpA) in aqueous solution, as obtained by NMR and restrained molecular dynamics.
  Protein Sci, 5, 1633-1647.  
  8845765 I.V.Kurinov, and R.W.Harrison (1996).
Two crystal structures of the leupeptin-trypsin complex.
  Protein Sci, 5, 752-758.
PDB codes: 1jrs 1jrt
  8844843 J.Doumen, M.Gonciarz, I.Zegers, R.Loris, L.Wyns, and J.Steyaert (1996).
A catalytic function for the structurally conserved residue Phe 100 of ribonuclease T1.
  Protein Sci, 5, 1523-1530.
PDB code: 1bir
8816770 M.Gerstein, and C.Chothia (1996).
Packing at the protein-water interface.
  Proc Natl Acad Sci U S A, 93, 10167-10172.  
8688423 O.Lequin, C.Albaret, F.Bontems, G.Spik, and J.Y.Lallemand (1996).
Solution structure of bovine angiogenin by 1H nuclear magnetic resonance spectroscopy.
  Biochemistry, 35, 8870-8880.
PDB code: 1gio
8758988 P.Friedhoff, B.Kolmes, O.Gimadutdinow, W.Wende, K.L.Krause, and A.Pingoud (1996).
Analysis of the mechanism of the Serratia nuclease using site-directed mutagenesis.
  Nucleic Acids Res, 24, 2632-2639.  
8749843 R.W.Harrison, D.Chatterjee, and I.T.Weber (1995).
Analysis of six protein structures predicted by comparative modeling techniques.
  Proteins, 23, 463-471.  
8710824 S.Mosimann, R.Meleshko, and M.N.James (1995).
A critical assessment of comparative molecular modeling of tertiary structures of proteins.
  Proteins, 23, 301-317.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.