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PDBsum entry 1afu

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protein Protein-protein interface(s) links
Hydrolase PDB id
1afu
Jmol
Contents
Protein chains
124 a.a. *
Waters ×83
* Residue conservation analysis
PDB id:
1afu
Name: Hydrolase
Title: Structure of ribonuclease a at 2.0 angstroms from monoclinic crystals
Structure: Ribonuclease a. Chain: a, b. Ec: 3.1.27.5
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas
Biol. unit: Monomer (from PDB file)
Resolution:
2.00Å     R-factor:   0.201     R-free:   0.285
Authors: D.D.Leonidas,K.R.Acharya
Key ref:
D.D.Leonidas et al. (1997). Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'-phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution. Biochemistry, 36, 5578-5588. PubMed id: 9154942 DOI: 10.1021/bi9700330
Date:
14-Mar-97     Release date:   18-Mar-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
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: 10.1021/bi9700330 Biochemistry 36:5578-5588 (1997)
PubMed id: 9154942  
 
 
Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'-phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution.
D.D.Leonidas, R.Shapiro, L.I.Irons, N.Russo, K.R.Acharya.
 
  ABSTRACT  
 
High-resolution (1.7 A) crystal structures have been determined for bovine pancreatic ribonuclease A (RNase A) complexed with 5'-diphosphoadenosine 3'-phosphate (ppA-3'-p) and 5'-diphosphoadenosine 2'-phosphate (ppA-2'-p), as well as for a native structure refined to 2.0 A. These nucleotide phosphates are the two most potent inhibitors of RNase A reported so far, with Ki values of 240 and 520 nM, respectively. The binding modes and conformations of ppA-3'-p and ppA-2'-p were found to differ markedly from those anticipated on the basis of earlier structures of RNase A complexes. The key difference is that the 5'-beta-phosphate rather than the 5'-alpha-phosphate of each inhibitor occupies the P1 phosphate binding site. As a consequence, the ribose moieties of the two nucleotides are shifted by approximately 2 A compared to the positions of their counterparts in earlier complexes, and the adenine rings are rotated into unusual syn conformations. Thus, the six-membered and five-membered rings of both adenines are reversed with respect to the others but nonetheless engage in extensive interactions with the residues that form the B2 purine binding site of RNase A. Despite the close structural similarity of the two inhibitors, the puckers of their furanose rings are different: C2'-endo and C3'-endo, respectively. Moreover, their 5'-alpha-phosphates and 3'(2')-monophosphates interact with largely different sets of RNase residues. The results of this crystallographic study emphasize the difficulties inherent in qualitative modeling of protein-inhibitor interactions and the compelling reasons for high-resolution structural studies in which quantitative design of improved inhibitors was enabled. The structures presented here provide a promising starting point for the rational design of tight-binding RNase inhibitors, which may be used as therapeutic agents in restraining the ribonucleolytic activities of RNase homologues such as angiogenin, eosinophil-derived neurotoxin, and eosinophil cationic protein.
 

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
21134128 U.Arnold, F.Leich, P.Neumann, H.Lilie, and R.Ulbrich-Hofmann (2011).
Crystal structure of RNase A tandem enzymes and their interaction with the cytosolic ribonuclease inhibitor.
  FEBS J, 278, 331-340.
PDB codes: 3mwq 3mwr 3mx8
  20124705 S.B.Larson, J.S.Day, C.Nguyen, R.Cudney, and A.McPherson (2010).
Structure of bovine pancreatic ribonuclease complexed with uridine 5'-monophosphate at 1.60 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 113-120.
PDB code: 3jw1
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.  
17581083 M.Lund, B.Jönsson, and C.E.Woodward (2007).
Implications of a high dielectric constant in proteins.
  J Chem Phys, 126, 225103.  
  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.  
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
15794557 A.Mahn, G.Zapata-Torres, and J.A.Asenjo (2005).
A theory of protein-resin interaction in hydrophobic interaction chromatography.
  J Chromatogr A, 1066, 81-88.  
16131486 A.N.Khan, and P.N.Lewis (2005).
Unstructured conformations are a substrate requirement for the Sir2 family of NAD-dependent protein deacetylases.
  J Biol Chem, 280, 36073-36078.  
15670155 C.L.Jenkins, N.Thiyagarajan, R.Y.Sweeney, M.P.Guy, B.R.Kelemen, K.R.Acharya, and R.T.Raines (2005).
Binding of non-natural 3'-nucleotides to ribonuclease A.
  FEBS J, 272, 744-755.
PDB codes: 1w4o 1w4p 1w4q
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
14726951 C.Hirsch, S.Misaghi, D.Blom, M.E.Pacold, and H.L.Ploegh (2004).
Yeast N-glycanase distinguishes between native and non-native glycoproteins.
  EMBO Rep, 5, 201-206.  
15067677 N.Basdevant, D.Borgis, and T.Ha-Duong (2004).
A semi-implicit solvent model for the simulation of peptides and proteins.
  J Comput Chem, 25, 1015-1029.  
14573867 D.D.Leonidas, G.B.Chavali, N.G.Oikonomakos, E.D.Chrysina, M.N.Kosmopoulou, M.Vlassi, C.Frankling, and K.R.Acharya (2003).
High-resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors.
  Protein Sci, 12, 2559-2574.
PDB codes: 1o0f 1o0h 1o0m 1o0n 1o0o
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
11876642 G.J.Swaminathan, D.E.Holloway, K.Veluraja, and K.R.Acharya (2002).
Atomic resolution (0.98 A) structure of eosinophil-derived neurotoxin.
  Biochemistry, 41, 3341-3352.
PDB code: 1gqv
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
11468363 D.D.Leonidas, G.B.Chavali, A.M.Jardine, S.Li, R.Shapiro, and K.R.Acharya (2001).
Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography.
  Protein Sci, 10, 1669-1676.
PDB codes: 1h52 1h53 1hby
11296285 N.E.Robinson, and A.B.Robinson (2001).
Prediction of protein deamidation rates from primary and three-dimensional structure.
  Proc Natl Acad Sci U S A, 98, 4367-4372.  
10944393 H.Ponstingl, K.Henrick, and J.M.Thornton (2000).
Discriminating between homodimeric and monomeric proteins in the crystalline state.
  Proteins, 41, 47-57.  
  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
10986462 S.Carr, D.Walker, R.James, C.Kleanthous, and A.M.Hemmings (2000).
Inhibition of a ribosome-inactivating ribonuclease: the crystal structure of the cytotoxic domain of colicin E3 in complex with its immunity protein.
  Structure, 8, 949-960.
PDB code: 1e44
10091597 E.H.Vatzaki, S.C.Allen, D.D.Leonidas, K.Trautwein-Fritz, J.Stackhouse, S.A.Benner, and K.R.Acharya (1999).
Crystal structure of a hybrid between ribonuclease A and bovine seminal ribonuclease--the basic surface, at 2.0 A resolution.
  Eur J Biochem, 260, 176-182.
PDB code: 1b6v
10329690 N.Russo, and R.Shapiro (1999).
Potent inhibition of mammalian ribonucleases by 3', 5'-pyrophosphate-linked nucleotides.
  J Biol Chem, 274, 14902-14908.  
9786875 B.Schneider, Y.W.Xu, J.Janin, M.Véron, and D.Deville-Bonne (1998).
3'-Phosphorylated nucleotides are tight binding inhibitors of nucleoside diphosphate kinase activity.
  J Biol Chem, 273, 28773-28778.
PDB code: 1bux
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.  
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.