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PDBsum entry 1w4o

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
1w4o
Jmol
Contents
Protein chains
124 a.a. *
Ligands
UA3
Waters ×200
* Residue conservation analysis
PDB id:
1w4o
Name: Hydrolase
Title: Binding of nonnatural 3'-nucleotides to ribonuclease a
Structure: Pancreatic ribonuclease a. Chain: a, b. Synonym: rnase 1, rnase a. Other_details: arabinouridine 3'-phosphate
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: pancreas
Resolution:
1.6Å     R-factor:   0.232     R-free:   0.248
Authors: C.L.Jenkins,N.Thiyagarajan,R.Y.Sweeney,M.P.Guy,B.R.Kelemen, K.R.Acharya,R.T.Raines
Key ref:
C.L.Jenkins et al. (2005). Binding of non-natural 3'-nucleotides to ribonuclease A. FEBS J, 272, 744-755. PubMed id: 15670155 DOI: 10.1111/j.1742-4658.2004.04511.x
Date:
27-Jul-04     Release date:   02-Feb-05    
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  

 

 
DOI no: 10.1111/j.1742-4658.2004.04511.x FEBS J 272:744-755 (2005)
PubMed id: 15670155  
 
 
Binding of non-natural 3'-nucleotides to ribonuclease A.
C.L.Jenkins, N.Thiyagarajan, R.Y.Sweeney, M.P.Guy, B.R.Kelemen, K.R.Acharya, R.T.Raines.
 
  ABSTRACT  
 
2'-Fluoro-2'-deoxyuridine 3'-phosphate (dU(F)MP) and arabinouridine 3'-phosphate (araUMP) have non-natural furanose rings. dU(F)MP and araUMP were prepared by chemical synthesis and found to have three- to sevenfold higher affinity than uridine 3'-phosphate (3'-UMP) or 2'-deoxyuridine 3'-phosphate (dUMP) for ribonuclease A (RNase A). These differences probably arise (in part) from the phosphoryl groups of 3'-UMP, dU(F)MP, and araUMP (pK(a) = 5.9) being more anionic than that of dUMP (pK(a) = 6.3). The three-dimensional structures of the crystalline complexes of RNase A with dUMP, dU(F)MP and araUMP were determined at < 1.7 A resolution by X-ray diffraction analysis. In these three structures, the uracil nucleobases and phosphoryl groups bind to the enzyme in a nearly identical position. Unlike 3'-UMP and dU(F)MP, dUMP and araUMP bind with their furanose rings in the preferred pucker. In the RNase A.araUMP complex, the 2'-hydroxyl group is exposed to the solvent. All four 3'-nucleotides bind more tightly to wild-type RNase A than to its T45G variant, which lacks the residue that interacts most closely with the uracil nucleobase. These findings illuminate in atomic detail the interaction of RNase A and 3'-nucleotides, and indicate that non-natural furanose rings can serve as the basis for more potent inhibitors of catalysis by RNase A.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Schematic representation of RNase A in complex with 3'-nucleotides. dUMP (5a), dark green; dU^FMP (5b), gold; araUMP (10), blue.
Figure 3.
Fig. 3. (A) S and N conformation of nucleosides. R = H favours the S conformation; R = OH,F favours the N conformation. (B) Stereodiagram of 3'-nucleotides in the RNase A·3'-nucleotide complexes, superimposed with respect to their uracil ring. dUMP (5a), dark green; dU^FMP (5b), gold; araUMP (10), blue.
 
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS J (2005, 272, 744-755) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21205197 N.Thiyagarajan, B.D.Smith, R.T.Raines, and K.R.Acharya (2011).
Functional and structural analyses of N-acylsulfonamide-linked dinucleoside inhibitors of RNase A.
  FEBS J, 278, 541-549.
PDB codes: 2xog 2xoi
  20124705 S.B.Larson, J.S.Day, C.Nguyen, R.Cudney, and A.McPherson (2010).
Structure of bovine pancreatic ribonuclease complexed with uridine 5'-monophosphate at 1.60 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 113-120.
PDB code: 3jw1
17327674 C.Mueller-Dieckmann, S.Panjikar, A.Schmidt, S.Mueller, J.Kuper, A.Geerlof, M.Wilmanns, R.K.Singh, P.A.Tucker, and M.S.Weiss (2007).
On the routine use of soft X-rays in macromolecular crystallography. Part IV. Efficient determination of anomalous substructures in biomacromolecules using longer X-ray wavelengths.
  Acta Crystallogr D Biol Crystallogr, 63, 366-380.
PDB codes: 2g4h 2g4i 2g4j 2g4k 2g4l 2g4m 2g4n 2g4o 2g4p 2g4q 2g4r 2g4s 2g4t 2g4u 2g4v 2g4w 2g4x 2g4y 2g4z 2g51 2g52 2g55 2ill
16730994 D.D.Leonidas, T.K.Maiti, A.Samanta, S.Dasgupta, T.Pathak, S.E.Zographos, and N.G.Oikonomakos (2006).
The binding of 3'-N-piperidine-4-carboxyl-3'-deoxy-ara-uridine to ribonuclease A in the crystal.
  Bioorg Med Chem, 14, 6055-6064.
PDB codes: 2g8q 2g8r
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.