RCSB PDB - 1AFK: CRYSTAL STRUCTURE OF RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE-3'-PHOSPHATE

 1AFK

CRYSTAL STRUCTURE OF RIBONUCLEASE A IN COMPLEX WITH 5'-DIPHOSPHOADENOSINE-3'-PHOSPHATE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.211 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'-phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution.

Leonidas, D.D.Shapiro, R.Irons, L.I.Russo, N.Acharya, K.R.

(1997) Biochemistry 36: 5578-5588

  • DOI: https://doi.org/10.1021/bi9700330
  • Primary Citation of Related Structures:  
    1AFK, 1AFL, 1AFU

  • PubMed Abstract: 

    High-resolution (1.7 A) crystal structures have been determined for bovine pancreatic ribonuclease A (RNase A) complexed with 5'-diphosphoadenosine 3'-phosphate (ppA-3'-p) and 5'-diphosphoadenosine 2'-phosphate (ppA-2'-p), as well as for a native structure refined to 2.0 A. These nucleotide phosphates are the two most potent inhibitors of RNase A reported so far, with Ki values of 240 and 520 nM, respectively. The binding modes and conformations of ppA-3'-p and ppA-2'-p were found to differ markedly from those anticipated on the basis of earlier structures of RNase A complexes. The key difference is that the 5'-beta-phosphate rather than the 5'-alpha-phosphate of each inhibitor occupies the P1 phosphate binding site. As a consequence, the ribose moieties of the two nucleotides are shifted by approximately 2 A compared to the positions of their counterparts in earlier complexes, and the adenine rings are rotated into unusual syn conformations. Thus, the six-membered and five-membered rings of both adenines are reversed with respect to the others but nonetheless engage in extensive interactions with the residues that form the B2 purine binding site of RNase A. Despite the close structural similarity of the two inhibitors, the puckers of their furanose rings are different: C2'-endo and C3'-endo, respectively. Moreover, their 5'-alpha-phosphates and 3'(2')-monophosphates interact with largely different sets of RNase residues. The results of this crystallographic study emphasize the difficulties inherent in qualitative modeling of protein-inhibitor interactions and the compelling reasons for high-resolution structural studies in which quantitative design of improved inhibitors was enabled. The structures presented here provide a promising starting point for the rational design of tight-binding RNase inhibitors, which may be used as therapeutic agents in restraining the ribonucleolytic activities of RNase homologues such as angiogenin, eosinophil-derived neurotoxin, and eosinophil cationic protein.


  • Organizational Affiliation

    School of Biology and Biochemistry, University of Bath, Claverton Down, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RIBONUCLEASE A
A, B
124Bos taurusMutation(s): 0 
EC: 3.1.27.5 (PDB Primary Data), 4.6.1.18 (UniProt)
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PAP
Query on PAP

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
3'-PHOSPHATE-ADENOSINE-5'-DIPHOSPHATE
C10 H16 N5 O13 P3
GBBWIZKLHXYJOA-KQYNXXCUSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PAP PDBBind:  1AFK Ki: 240 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.211 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.54α = 90
b = 33.36β = 90.09
c = 73.25γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-03-18
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-02
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2024-10-30
    Changes: Data collection, Structure summary