1OKV

Cyclin A binding groove inhibitor H-Arg-Arg-Leu-Ile-Phe-NH2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Insights Into Cyclin Groove Recognition. Complex Crystal Structures and Inhibitor Design Through Ligand Exchange

Kontopidis, G.Andrews, M.Mcinnes, C.Cowan, A.Powers, H.Innes, L.Plater, A.Griffiths, G.Paterson, D.Zheleva, D.Lane, D.Green, S.Walkinshaw, M.Fischer, P.

(2003) Structure 11: 1537

  • DOI: https://doi.org/10.1016/j.str.2003.11.006
  • Primary Citation of Related Structures:  
    1OKV, 1OKW, 1OL1, 1OL2

  • PubMed Abstract: 

    Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) activity through blocking of the substrate recognition site in the cyclin A subunit has been demonstrated to be an effective method for inducing apoptosis in tumor cells. We have used the cyclin binding motif (CBM) present in the tumor suppressor proteins p21(WAF1) and p27(KIP1) as a template to optimize the minimal sequence necessary for CDK2/CA inhibition. A series of peptides were prepared, containing nonnatural amino acids, which possess nano- to micromolar CDK2-inhibitory activity. Here we present X-ray structures of the protein complex CDK2/CA, together with the cyclin groove-bound peptides H-Ala-Ala-Abu-Arg-Ser-Leu-Ile-(p-F-Phe)-NH(2) (peptide 1), H-Arg-Arg-Leu-Ile-Phe-NH(2) (peptide 2), Ac-Arg-Arg-Leu-Asn-(m-Cl-Phe)-NH(2) (peptide 3), H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH(2) (peptide 4), and H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH(2) (peptide 5). Some of the peptide complexes presented here were obtained through the novel technique of ligand exchange within protein crystals. This method may find general application for obtaining complex structures of proteins with surface-bound ligands.


  • Organizational Affiliation

    Cyclacel Ltd., James Lindsay Place, Dundee DD1 5JJ, Scotland, United Kingdom. gkontopidis@cyclacel.com


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CELL DIVISION PROTEIN KINASE 2
A, C
298Homo sapiensMutation(s): 0 
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
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLIN A2
B, D
260Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P20248 (Homo sapiens)
Explore P20248 
Go to UniProtKB:  P20248
PHAROS:  P20248
GTEx:  ENSG00000145386 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20248
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
H-ARG-ARG-LEU-ILE-PHE-NH2
E, F
6synthetic constructMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.201 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.193α = 90
b = 113.879β = 90
c = 155.274γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKLdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.2: 2015-09-16
    Changes: Source and taxonomy
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Refinement description