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PDBsum entry 1o0m

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
1o0m
Jmol
Contents
Protein chains
124 a.a. *
Ligands
U2P ×2
Waters ×399
* Residue conservation analysis
PDB id:
1o0m
Name: Hydrolase
Title: Ribonuclease a in complex with uridine-2'-phosphate
Structure: Ribonuclease pancreatic. Chain: a, b. Synonym: ribonuclease a. Ec: 3.1.27.5
Source: Bos taurus. Cattle. Organism_taxid: 9913
Resolution:
1.50Å     R-factor:   0.211     R-free:   0.244
Authors: D.D.Leonidas,N.G.Oikonomakos,E.D.Chrysina,M.N.Kosmopoulou, M.Vlassi
Key ref:
D.D.Leonidas et al. (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. PubMed id: 14573867 DOI: 10.1110/ps.03196603
Date:
24-Feb-03     Release date:   09-Dec-03    
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

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     nucleic acid binding     6 terms  

 

 
DOI no: 10.1110/ps.03196603 Protein Sci 12:2559-2574 (2003)
PubMed id: 14573867  
 
 
High-resolution crystal structures of ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors.
D.D.Leonidas, G.B.Chavali, N.G.Oikonomakos, E.D.Chrysina, M.N.Kosmopoulou, M.Vlassi, C.Frankling, K.R.Acharya.
 
  ABSTRACT  
 
The crystal structures of bovine pancreatic ribonuclease A (RNase A) in complex with 3',5'-ADP, 2',5'-ADP, 5'-ADP, U-2'-p and U-3'-p have been determined at high resolution. The structures reveal that each inhibitor binds differently in the RNase A active site by anchoring a phosphate group in subsite P1. The most potent inhibitor of all five, 5'-ADP (Ki = 1.2 microM), adopts a syn conformation (in contrast to 3',5'-ADP and 2',5'-ADP, which adopt an anti), and it is the beta- rather than the alpha-phosphate group that binds to P1. 3',5'-ADP binds with the 5'-phosphate group in P1 and the adenosine in the B2 pocket. Two different binding modes are observed in the two RNase A molecules of the asymmetric unit for 2',5'-ADP. This inhibitor binds with either the 3' or the 5' phosphate groups in subsite P1, and in each case, the adenosine binds in two different positions within the B2 subsite. The two uridilyl inhibitors bind similarly with the uridine moiety in the B1 subsite but the placement of a different phosphate group in P1 (2' versus 3') has significant implications on their potency against RNase A. Comparative structural analysis of the RNase A, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and human angiogenin (Ang) complexes with these and other phosphonucleotide inhibitors provides a wealth of information for structure-based design of inhibitors specific for each RNase. These inhibitors could be developed to therapeutic agents that could control the biological activities of EDN, ECP, and ANG, which play key roles in human pathologies.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. (A, B, D, E, and F) Diagrams of the interactions between RNase A molecule I of the asymmetric unit and 3',5'-ADP, 2',5'-ADP, 5'-ADP, 2' UMP, and 3' UMP, respectively. (C) Diagram of the interactions between RNase A and 2',5'-ADP in molecule II of the asymmetric unit. Molecules I and II refer to the two RNase A molecules in the asymmetric unit. Residues are drawn as ball-and-stick models and water molecules as white spheres. Hydrogen bonds are indicated as dashed lines.
Figure 5.
Figure 5. A schematic representation of RNase A in complex with 3',5'-ADP (in green). The inhibitors 2',5'-ADP (in gray and cyan from molecules I and II of the asymmetric unit, respectively), 5'-ADP (in red), U-3'-p (in magenta) and U-2'-p (in yellow) are also shown.
 
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 2559-2574) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  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.  
18565758 S.Yin, Y.Xie, and J.A.Loo (2008).
Mass spectrometry of protein-ligand complexes: enhanced gas-phase stability of ribonuclease-nucleotide complexes.
  J Am Soc Mass Spectrom, 19, 1199-1208.  
17612625 C.N.N'soukpoé-Kossi, C.Ragi, and H.A.Tajmir-Riahi (2007).
RNase A - tRNA binding alters protein conformation.
  Biochem Cell Biol, 85, 311-318.  
  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.  
17417947 S.S.Pachouri, R.C.Sobti, P.Kaur, and J.Singh (2007).
Contrasting impact of DNA repair gene XRCC1 polymorphisms Arg399Gln and Arg194Trp on the risk of lung cancer in the north-Indian population.
  DNA Cell Biol, 26, 186-191.  
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
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
15768372 G.Sundqvist, K.Benkestock, and J.Roeraade (2005).
Investigation of multiple binding sites on ribonuclease A using nano-electrospray ionization mass spectrometry.
  Rapid Commun Mass Spectrom, 19, 1011-1016.  
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 code is shown on the right.