3LXO

The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.141 
  • R-Value Observed: 0.145 

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Literature

The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate provides further insight into ligand binding.

Doucet, N.Jayasundera, T.B.Simonovic, M.Loria, J.P.

(2010) Proteins 78: 2459-2468

  • DOI: https://doi.org/10.1002/prot.22754
  • Primary Citation of Related Structures:  
    3LXO

  • PubMed Abstract: 

    Thymidine-3'-monophosphate (3'-TMP) is a competitive inhibitor analogue of the 3'-CMP and 3'-UMP natural product inhibitors of bovine pancreatic ribonuclease A (RNase A). Isothermal titration calorimetry experiments show that 3'-TMP binds the enzyme with a dissociation constant (K(d)) of 15 microM making it one of the strongest binding members of the five natural bases found in nucleic acids (A, C, G, T, and U). To further investigate the molecular properties of this potent natural affinity, we have determined the crystal structure of bovine pancreatic RNase A in complex with 3'-TMP at 1.55 A resolution and we have performed NMR binding experiments with 3'-CMP and 3'-TMP. Our results show that binding of 3'-TMP is very similar to other natural and non-natural pyrimidine ligands, demonstrating that single nucleotide affinity is independent of the presence or absence of a 2'-hydroxyl on the ribose moiety of pyrimidines and suggesting that the pyrimidine binding subsite of RNase A is not a significant contributor of inhibitor discrimination. Accumulating evidence suggests that very subtle structural, chemical, and potentially motional variations contribute to ligand discrimination in this enzyme.


  • Organizational Affiliation

    Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribonuclease pancreatic124Bos taurusMutation(s): 0 
EC: 3.1.27.5
UniProt
Find proteins for P61823 (Bos taurus)
Explore P61823 
Go to UniProtKB:  P61823
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61823
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
T3P
Query on T3P

Download Ideal Coordinates CCD File 
B [auth A]THYMIDINE-3'-PHOSPHATE
C10 H15 N2 O8 P
XXYIANZGUOSQHY-XLPZGREQSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
T3P PDBBind:  3LXO Kd: 1.50e+4 (nM) from 1 assay(s)
Binding MOAD:  3LXO Kd: 1.50e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.141 
  • R-Value Observed: 0.145 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.592α = 90
b = 64.592β = 90
c = 65.364γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance