3RQ7

Polo-like kinase 1 Polo box domain in complex with a C6H5(CH2)8-derivatized peptide inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.154 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel.

Liu, F.Park, J.E.Qian, W.J.Lim, D.Graber, M.Berg, T.Yaffe, M.B.Lee, K.S.Burke, T.R.

(2011) Nat Chem Biol 7: 595-601

  • DOI: https://doi.org/10.1038/nchembio.614
  • Primary Citation of Related Structures:  
    3RQ7

  • PubMed Abstract: 

    We obtained unanticipated synthetic byproducts from alkylation of the δ(1) nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C(6)H(5)(CH(2))(8)- group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1 PBD with affinity equal to that of the non-PEGylated parent but showed markedly less interaction with the PBDs of the two closely related proteins Plk2 and Plk3. Treatment of cultured cells with this PEGylated peptide resulted in delocalization of Plk1 from centrosomes and kinetochores and in chromosome misalignment that effectively induced mitotic block and apoptotic cell death. This work provides insights that might advance efforts to develop Plk1 PBD-binding inhibitors as potential Plk1-specific anticancer agents.


  • Organizational Affiliation

    Chemical Biology Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase PLK1237Homo sapiensMutation(s): 0 
Gene Names: PLK1PLK
EC: 2.7.11.21
UniProt & NIH Common Fund Data Resources
Find proteins for P53350 (Homo sapiens)
Explore P53350 
Go to UniProtKB:  P53350
PHAROS:  P53350
GTEx:  ENSG00000166851 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53350
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C6H5(CH2)8-derivatized peptide inhibitor7N/AMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
56A
Query on 56A
B
L-PEPTIDE LINKINGC20 H29 N3 O2HIS
TPO
Query on TPO
B
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.55 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.154 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 35.337α = 90
b = 51.21β = 101
c = 57.963γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-07-20
    Type: Initial release
  • Version 1.1: 2011-08-03
    Changes: Database references
  • Version 1.2: 2011-08-31
    Changes: Database references
  • Version 1.3: 2012-10-10
    Changes: Structure summary
  • Version 1.4: 2012-12-12
    Changes: Other