1PF8

Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2.

Moshinsky, D.J.Bellamacina, C.R.Boisvert, D.C.Huang, P.Hui, T.Jancarik, J.Kim, S.H.Rice, A.G.

(2003) Biochem Biophys Res Commun 310: 1026-1031

  • DOI: https://doi.org/10.1016/j.bbrc.2003.09.114
  • Primary Citation of Related Structures:  
    1PF8

  • PubMed Abstract: 

    SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.


  • Organizational Affiliation

    SUGEN, Inc., South San Francisco, CA 94080, USA. deborah.moshinsky@pharma.novartis.com


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: 2.7.1.37
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
SU9
Query on SU9

Download Ideal Coordinates CCD File 
B [auth A](3Z)-3-(1H-IMIDAZOL-5-YLMETHYLENE)-5-METHOXY-1H-INDOL-2(3H)-ONE
C13 H11 N3 O2
QNUKRWAIZMBVCU-WCIBSUBMSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SU9 PDBBind:  1PF8 Ki: 31 (nM) from 1 assay(s)
BindingDB:  1PF8 IC50: min: 22, max: 110 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.753α = 90
b = 72.306β = 90
c = 71.944γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
GLRFphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-23
    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: 2014-04-16
    Changes: Data collection
  • Version 1.4: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description