1NDV

Crystal Structure of Adenosine Deaminase complexed with FR117016


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization

Terasaka, T.Kinoshita, T.Kuno, M.Nakanishi, I.

(2004) J Am Chem Soc 126: 34-35

  • DOI: https://doi.org/10.1021/ja038606l
  • Primary Citation of Related Structures:  
    1NDV, 1NDW, 1NDY, 1NDZ

  • PubMed Abstract: 

    We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM) non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational hybridization of two structurally distinct leads. Two micromolar inhibitors were discovered by a parallel rational design and random screening program, and individual crystal structures of bovine ADA in complexation with these inhibitors revealed several unknown binding sites and distinct binding modes. Using this information as the starting point, highly effective lead hybridization was achieved in only two structure-based drug design iterations. The conceptual approach illustrated by this example promises to be broadly useful in the search for new chemical entities and can contribute greatly to improve the overall efficiency and speed of drug discovery.


  • Organizational Affiliation

    Medicinal Chemistry Research Laboratories, Basic Research Laboratories, and Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Adenosine deaminase356Bos taurusMutation(s): 0 
EC: 3.5.4.4
UniProt
Find proteins for P56658 (Bos taurus)
Explore P56658 
Go to UniProtKB:  P56658
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56658
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FR0
Query on FR0

Download Ideal Coordinates CCD File 
C [auth A]N''-(4-(5-((1H-BENZIMIDAZOL-2-YLAMINO)METHYL)-2-THIENYL)-1,3-THIAZOL-2-YL)GUANIDINE
C16 H15 N7 S2
CKJGKHXCUDWFDC-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FR0 PDBBind:  1NDV Ki: 1200 (nM) from 1 assay(s)
BindingDB:  1NDV Ki: 1200 (nM) from 1 assay(s)
IC50: 700 (nM) from 1 assay(s)
Binding MOAD:  1NDV Ki: 1200 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.230 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.03α = 90
b = 78.03β = 90
c = 136.66γ = 90
Software Package:
Software NamePurpose
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-09
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references, Derived calculations