1PXI

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 4-(2,5-Dichloro-thiophen-3-yl)-pyrimidin-2-ylamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop

Wu, S.Y.McNae, I.Kontopidis, G.McClue, S.J.McInnes, C.Stewart, K.J.Wang, S.Zheleva, D.I.Marriage, H.Lane, D.P.Taylor, P.Fischer, P.M.Walkinshaw, M.D.

(2003) Structure 11: 399-410

  • DOI: https://doi.org/10.1016/s0969-2126(03)00060-1
  • Primary Citation of Related Structures:  
    1PW2, 1PXI, 1PXJ, 1PXK, 1PXL

  • PubMed Abstract: 

    A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds was discovered with the new database-mining program LIDAEUS through in silico screening. Four compounds with IC(50) values ranging from 17 to 0.9 microM were selected for X-ray crystal analysis. Two distinct binding modes are observed, one of which resembles the hydrogen bonding pattern of bound ATP. In the second binding mode, the ligands trigger a conformational change in the activation T loop by inducing movement of Lys(33) and Asp(145) side chains. The family of molecules discovered provides an excellent starting point for the design and synthesis of tight binding inhibitors, which may lead to a new class of antiproliferative drugs.


  • Organizational Affiliation

    Structural Biochemistry Group, The University of Edinburgh, Michael Swann Building, King's Buildings, EH9 3JR, Edinburgh, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2298Homo sapiensMutation(s): 0 
Gene Names: CDK2
EC: 2.7.1
UniProt & NIH Common Fund Data Resources
Find proteins for P24941 (Homo sapiens)
Explore P24941 
Go to UniProtKB:  P24941
PHAROS:  P24941
GTEx:  ENSG00000123374 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP24941
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CK1
Query on CK1

Download Ideal Coordinates CCD File 
B [auth A]4-(2,5-DICHLOROTHIEN-3-YL)PYRIMIDIN-2-AMINE
C8 H5 Cl2 N3 S
PAPYICJQRHSQGK-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CK1 PDBBind:  1PXI IC50: 1.70e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.499α = 90
b = 71.404β = 90
c = 72.356γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-09
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description