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PDBsum entry 3d8y

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3d8y
Jmol
Contents
Protein chains
124 a.a. *
Ligands
T3S
FLC ×2
Waters ×213
* Residue conservation analysis
PDB id:
3d8y
Name: Hydrolase
Title: Rnase a- 5'-deoxy-5'-n-piperidinothymidine complex
Structure: Ribonuclease pancreatic. Chain: a, b. Synonym: ribonuclease a, rnase 1, rnase a. Ec: 3.1.27.5
Source: Bos taurus. Bovine. Organism_taxid: 9913. Tissue: pancreas
Resolution:
1.72Å     R-factor:   0.191     R-free:   0.230
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
Date:
26-May-08     Release date:   10-Feb-09    
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  

 

 
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.
 
  ABSTRACT  
 
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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