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PDBsum entry 3djv

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3djv
Jmol
Contents
Protein chains
124 a.a. *
Ligands
C3P ×2
Waters ×309
* Residue conservation analysis
PDB id:
3djv
Name: Hydrolase
Title: Bovine seminal ribonuclease- cytidine 3' phosphate complex
Structure: Seminal ribonuclease. Chain: a, b. Synonym: seminal rnase, s-rnase, ribonuclease bs-1. Ec: 3.1.27.5
Source: Bos taurus. Bovine. Organism_taxid: 9913
Resolution:
1.60Å     R-factor:   0.178     R-free:   0.204
Authors: K.Dossi,D.D.Leonidas,S.E.Zographos,N.G.Oikonomakos
Key ref: K.Dossi et al. (2009). Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors. Eur J Med Chem, 44, 4496-4508. PubMed id: 19643512 DOI: 10.1016/j.ejmech.2009.06.039
Date:
24-Jun-08     Release date:   30-Jun-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00669  (RNS_BOVIN) -  Seminal ribonuclease
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     catalytic activity     8 terms  

 

 
DOI no: 10.1016/j.ejmech.2009.06.039 Eur J Med Chem 44:4496-4508 (2009)
PubMed id: 19643512  
 
 
Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors.
K.Dossi, V.G.Tsirkone, J.M.Hayes, J.Matousek, P.Poucková, J.Soucek, M.Zadinova, S.E.Zographos, D.D.Leonidas.
 
  ABSTRACT  
 
Bovine seminal ribonuclease (BS-RNase) is a 27kDa homodimeric enzyme and a member of the pancreatic RNase A superfamily. It is the only RNase with a quaternary structure and it is a mixture of two dimeric forms. In the most abundant form the active site is formed by the swapping of the N-terminal segments. BS-RNase is a potent antitumor agent with severe side effects such as aspermatogenicity, and immunosuppression. As a first step towards the design of potent inhibitors of this enzyme we mapped its active site through the study of the binding of uridine 2'-phosphate (U2'p), uridine 3'-phosphate (U3'p), uridine 5'-diphosphate (UDP), cytidine 3'-phosphate (C3'p), and cytidine 5-phosphate (C5'p), by kinetics, and X-ray crystallography. These phosphonucleotides are potent inhibitors with C3'p being the most potent with a K(i) value of 22 microM. Absorption, distribution, metabolism, and excretion pharmacokinetic property predictions reveal U2'p, U3'p, and C5'p as the most promising with respect to oral bioavailability. In vivo studies on the aspermatogenic effect have shown that C3'p and C5'p inhibit significantly this biological action of BS-RNase.