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PDBsum entry 1ymn

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protein links
Hydrolase PDB id
1ymn
Jmol
Contents
Protein chain
124 a.a. *
Waters ×209
* Residue conservation analysis
PDB id:
1ymn
Name: Hydrolase
Title: The study of reductive unfolding pathways of rnase a (y92l mutant)
Structure: Ribonuclease pancreatic. Chain: a. Synonym: rnase 1, rnase a. Engineered: yes. Mutation: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: rnase1, rns1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.45Å     R-factor:   0.193     R-free:   0.219
Authors: G.Xu,M.Narayan,I.Kurinov,D.R.Ripoll,E.Welker,M.Khalili, S.E.Ealick,H.A.Scheraga
Key ref: G.Xu et al. (2006). A localized specific interaction alters the unfolding pathways of structural homologues. J Am Chem Soc, 128, 1204-1213. PubMed id: 16433537 DOI: 10.1021/ja055313e
Date:
21-Jan-05     Release date:   31-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
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 1 residue position (black cross)

 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  

 

 
DOI no: 10.1021/ja055313e J Am Chem Soc 128:1204-1213 (2006)
PubMed id: 16433537  
 
 
A localized specific interaction alters the unfolding pathways of structural homologues.
G.Xu, M.Narayan, I.Kurinov, D.R.Ripoll, E.Welker, M.Khalili, S.E.Ealick, H.A.Scheraga.
 
  ABSTRACT  
 
Reductive unfolding studies of proteins are designed to provide information about intramolecular interactions that govern the formation (and stabilization) of the native state and about folding/unfolding pathways. By mutating Tyr92 to G, A, or L in the model protein, bovine pancreatic ribonuclease A, and through analysis of temperature factors and molecular dynamics simulations of the crystal structures of these mutants, it is demonstrated that the markedly different reductive unfolding rates and pathways of ribonuclease A and its structural homologue onconase can be attributed to a single, localized, ring-stacking interaction between Tyr92 and Pro93 in the bovine variant. The fortuitous location of this specific stabilizing interaction in a disulfide-bond-containing loop region of ribonuclease A results in the localized modulation of protein dynamics that, in turn, enhances the susceptibility of the disulfide bond to reduction leading to an alteration in the reductive unfolding behavior of the homologues. These results have important implications for folding studies involving topological determinants to obtain folding/unfolding rates and pathways, for protein structure-function prediction through fold recognition, and for predicting proteolytic cleavage sites.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19325988 C.David, S.Foley, and M.Enescu (2009).
Protein S-S bridge reduction: a Raman and computational study of lysozyme interaction with TCEP.
  Phys Chem Chem Phys, 11, 2532-2542.  
19344116 R.F.Gahl, L.Pradeep, C.R.Siegel, G.Xu, and H.A.Scheraga (2009).
Effects of tyrosine mutations on the conformational and oxidative folding of ribonuclease a: a comparative study.
  Biochemistry, 48, 3887-3893.  
19825371 W.Ardelt, B.Ardelt, and Z.Darzynkiewicz (2009).
Ribonucleases as potential modalities in anticancer therapy.
  Eur J Pharmacol, 625, 181-189.  
18322931 C.David, S.Foley, C.Mavon, and M.Enescu (2008).
Reductive unfolding of serum albumins uncovered by Raman spectroscopy.
  Biopolymers, 89, 623-634.  
17868092 G.R.Marshall, J.A.Feng, and D.J.Kuster (2008).
Back to the future: ribonuclease A.
  Biopolymers, 90, 259-277.  
18491388 J.Martin, L.Regad, C.Etchebest, and A.C.Camproux (2008).
Taking advantage of local structure descriptors to analyze interresidue contacts in protein structures and protein complexes.
  Proteins, 73, 672-689.  
18521887 N.Izumikawa, S.Nishikori, M.Vestergaard, T.Hamada, Y.Hagihara, N.Yumoto, K.Shiraki, and M.Takagi (2008).
Effect of phospholipids on conformational structure of bovine pancreatic trypsin inhibitor (BPTI) and its thermolabile mutants.
  Biopolymers, 89, 873-880.  
17920720 S.Brocchini, A.Godwin, S.Balan, J.W.Choi, M.Zloh, and S.Shaunak (2008).
Disulfide bridge based PEGylation of proteins.
  Adv Drug Deliv Rev, 60, 3.  
18673287 W.Ardelt, K.Shogen, and Z.Darzynkiewicz (2008).
Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes.
  Curr Pharm Biotechnol, 9, 215-225.  
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.