2BZS

Binding of anti-cancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history. 


Literature

Binding of the Anticancer Prodrug Cb1954 to the Activating Enzyme Nqo2 Revealed by the Crystal Structure of Their Complex.

Abu Khader, M.M., Heap, J.T., De Matteis, C., Kellam, B., Doughty, S.W., Minton, N., Paoli, M.

(2005) J Med Chem 48: 7714

  • DOI: https://doi.org/10.1021/jm050730n
  • Primary Citation of Related Structures:  
    2BZS

  • PubMed Abstract: 

    CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.

    • Organizational Affiliation: 

    School of Pharmacy and The Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NRH DEHYDROGENASE [QUINONE] 2
A, B
236Homo sapiensMutation(s): 0 
EC: 1.6.99 (PDB Primary Data), 1.10.5.1 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P16083 (Homo sapiens)
Explore P16083 
Go to UniProtKB:  P16083
PHAROS:  P16083
GTEx:  ENSG00000124588 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16083
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.83α = 90
b = 106.11β = 90
c = 61.65γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-09-23
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-12-12
    Changes: Advisory, Data collection, Structure summary
  • Version 1.4: 2023-12-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Other, Refinement description, Structure summary