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PDBsum entry 3fl0

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3fl0
Jmol
Contents
Protein chains
124 a.a. *
Ligands
CGP
Waters ×228
* Residue conservation analysis
PDB id:
3fl0
Name: Hydrolase
Title: X-ray structure of the non covalent swapped form of the q28l/k31c/s32c mutant of bovine pancreatic ribonuclease in complex with 2'-deoxycytidine-2'-deoxyguanosine-3',5'- monophosphate
Structure: Ribonuclease pancreatic. Chain: a, b. Synonym: ribonuclease, rnase 1, rnase a. Engineered: yes. Mutation: yes
Source: Bos taurus. Bovine. Organism_taxid: 9913. Gene: rnase1, rns1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.94Å     R-factor:   0.174     R-free:   0.227
Authors: A.Merlino,I.Russo Krauss,M.Perillo,C.A.Mattia,C.Ercole, D.Picone,A.Vergara,F.Sica
Key ref: A.Merlino et al. (2009). Toward an antitumor form of bovine pancreatic ribonuclease: the crystal structure of three noncovalent dimeric mutants. Biopolymers, 91, 1029-1037. PubMed id: 19280639
Date:
18-Dec-08     Release date:   24-Mar-09    
PROCHECK
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 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
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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     6 terms  

 

 
Biopolymers 91:1029-1037 (2009)
PubMed id: 19280639  
 
 
Toward an antitumor form of bovine pancreatic ribonuclease: the crystal structure of three noncovalent dimeric mutants.
A.Merlino, I.Russo Krauss, M.Perillo, C.A.Mattia, C.Ercole, D.Picone, A.Vergara, F.Sica.
 
  ABSTRACT  
 
The cytotoxic action of bovine seminal ribonuclease (BS-RNase) depends on its noncovalent swapped dimeric form (NCD-BS), which presents a compact structure that allows the molecule to escape ribonuclease inhibitor (RI). A key role in the acquisition of this structure has been attributed to the concomitant presence of a proline in position 19 and a leucine in position 28. The introduction of Leu28, Cys31, and Cys32 and, in addition, of Pro19 in the sequence of bovine pancreatic ribonuclease (RNase A) has produced two dimeric variants LCC and PLCC, which do exhibit a cytotoxic activity, though at a much lower level than BS-RNase. The crystal structure analysis of the noncovalent swapped form (NCD) of LCC and PLCC, complexed with the substrate analogue 2 '-deoxycytidylyl(3 ',5 ')-2 '-deoxyguanosine, has revealed that, differently from NCD-BS, the dimers adopt an opened quaternary structure, with the two Leu residues fully exposed to the solvent, that does not hinder the binding of RI. Similar results have been obtained for a third mutant of the pancreatic enzyme, engineered with the hinge peptide sequence of the seminal enzyme (residues 16-22) and the two cysteines in position 31 and 32, but lacking the hydrophobic Leu residue in position 28. The comparison of these three structures with those previously reported for other ribonuclease swapped dimers strongly suggests that, in addition to Pro19 and Leu28, the presence of a glycine at the N-terminal end of the hinge peptide is also important to push the swapped form of RNase A dimer into the compact quaternary organization observed for NCD-BS.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21122069 C.Giancola, C.Ercole, I.Fotticchia, R.Spadaccini, E.Pizzo, G.D'Alessio, and D.Picone (2011).
Structure-cytotoxicity relationships in bovine seminal ribonuclease: new insights from heat and chemical denaturation studies on variants.
  FEBS J, 278, 111-122.  
20843477 E.F.Fang, and T.B.Ng (2011).
Ribonucleases of different origins with a wide spectrum of medicinal applications.
  Biochim Biophys Acta, 1815, 65-74.  
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