PDBsum entry 3d6o

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Hydrolase PDB id
Protein chains
124 a.a. *
Waters ×313
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The rnase a- 5'-deoxy-5'-n-(ethyl isonipecotatyl)uridine com
Structure: Ribonuclease pancreatic. Chain: a, b. Synonym: rnase 1, rnase a. Ec:
Source: Bos taurus. Bovine. Organism_taxid: 9913
1.58Å     R-factor:   0.188     R-free:   0.227
Authors: D.D.Leonidas,S.E.Zographos,N.G.Oikonomakos
Key ref: A.Samanta et al. (2009). Morpholino, piperidino, and pyrrolidino derivatives of pyrimidine nucleosides as inhibitors of ribonuclease A: synthesis, biochemical, and crystallographic evaluation. J Med Chem, 52, 932-942. PubMed id: 19173562 DOI: 10.1021/jm800724t
20-May-08     Release date:   10-Feb-09    
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Protein chains
Pfam   ArchSchema ?
P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic
150 a.a.
124 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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/jm800724t J Med Chem 52:932-942 (2009)
PubMed id: 19173562  
Morpholino, piperidino, and pyrrolidino derivatives of pyrimidine nucleosides as inhibitors of ribonuclease A: synthesis, biochemical, and crystallographic evaluation.
A.Samanta, D.D.Leonidas, S.Dasgupta, T.Pathak, S.E.Zographos, N.G.Oikonomakos.
Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P(1), where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogenin, which is implicated in tumor induced neovascularization.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420869 A.Samanta, S.Dasgupta, and T.Pathak (2011).
5'-Modified pyrimidine nucleosides as inhibitors of ribonuclease A.
  Bioorg Med Chem, 19, 2478-2484.  
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