Crystal structure of human DT-diaphorase: A model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)

Journal of Medicinal Chemistry

Volumn 42, Issue 21, 1999, Pages 4325-4330

  Skelly, Jane V ^a   Sanderson, Mark R ^a   Suter, David A ^a   Baumann, Ulrich ^a   Read, Martin A ^a   Gregory, David S J ^a   Bennett, Matthew ^a   Hobbs, Stephen M ^b   Neidle, Stephen ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; CYTOTOXIC AGENT; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE);

ANIMAL CELL; ARTICLE; CRYSTAL STRUCTURE; DRUG BINDING; DRUG CYTOTOXICITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND; MOLECULAR INTERACTION; MOLECULAR MODEL; NONHUMAN; RAT;

AMINO ACID SEQUENCE; ANIMALS; ANTINEOPLASTIC AGENTS; AZIRIDINES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NAD(P)H DEHYDROGENASE (QUINONE); PRODRUGS; RATS;

EID: 0032741789     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991060m     Document Type: Article

References (27)

1. Ernster, L. DT diaphoraae - a Historical Review. Chem. Scripta 1987, 27A, 1-13.
2. Riley, R. J.; Workman, P. DT-diaphorase and Cancer Chemotherapy. Biochem. Pharmacol. 1992, 43, 1657-1669.
3. De Long, M. J.; Prochaska, H. J.; Talalay, P. Induction of NAD-(P)H:Quinone Reductase in Murine Hepatoma Cells by Phenolic Antioxidants, Azo Dyes and Other Chemoprotectors: A Model System for the Study of Anticarcinogens. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 787-791.
4. Schlager, J. J.; Powis, G. Cytosolic NAD(P)H: (Quinone Acceptor) Oxidoreductase in Human Normal and Tumour Tissue: Effects of Cigarette Smoking and Alcohol. Int. J. Cancer 1990, 45, 403-409.
5. Knox, R. J.; Friedlos, F.; Boland, M. P. The Bioactivation of CB1954 and its Use as a Prodrug in Antibody-Directed Prodrug Therapy (ADEPT). Cancer Metastasis Rev. 1993, 12, 195-212.
6. Boland, M. P.; Knox, R. J.; Roberts, J. J. The Differences in Kinetics of Rat and Human DT-diaphorase result in a Differential Sensitivity of Derived Cell Lines to CB1954 (5-(Aziridin-1-yl)-2,4-Dinitrobenzamide). Biochem. Pharmacol. 1991, 41, 867-875.
7. Mikami, K.; Naito, M.; Tomida, A.; Yamada, M.; Sirakusa, T.; Tsurua, T. DT Diaphorase as a Critical Determinant of Sensitivity to Mitomycin C in Human Colon and Gastric Carcinoma Cell Lines. Cancer Res. 1996, 56, 2823-2826.
8. Hu, L.-T.; Stamberg, J.; Pan, S.-S. The NAD(P)H:Quinone Oxidoreductase Locus in Human Colon Carcinoma HCT 116 Cells Resistant to Mitomycin C. Cancer Res. 1996, 56, 5253-5259.
9. Robertson, J. A.; Chen, H. C.; Nebert, D. W. NAD(P)H: Menadione Oxidoreductase: Novel Purification of the Enzyme, cDNA, and Complete Amino Acid Sequence, and Gene Regulation. J. Biol. Chem. 1986, 261, 15794-15799.
10. Byron, O.; Mistry, P.; Suter, D. A.; Skelly, J. V. DT-Diaphorase Exists as a Dimer-Tetramer Equilibrium in Solution. Eur. Biophys. J. 1997, 25, 423-430.
11. Chen, S.; Deng, P. S. K.; Bailey, J. M.; Sweiderek, K. M. A Two-domain Structure for the Two Subunits of NAD(P)H Quinone Acceptor Oxidoreductase. Protein Sci. 1994, 3, 51-57.
12. Li, R.; Bianchet, M.; Talalay, P.; Amzel, L. M. The Three-Dimensional Structureof NAD(P)H: Quinone Reductase, a Flavoprotein Involved in Cancer Chemoprotection and Chemotherapy: Mechanism of the Two-Electron Reduction. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8846-8850.
13. Siegel, D.; Gibson, N. W.; Prusch, P. C.; Ross, D. Metabolism of Mitomycin C by DT diaphorase: Role in Mitomycin C-Induced DNA Damage. Cancer Res. 1990, 50, 7483-7489.
14. Smitskamp-Wilms, E.; Hendriks, H. R.; Peters, G. J. Development, Pharmacology, Role of DT-Diaphorase and Prospects of Indoloquinone EO9. Gen. Pharmacol. 1996, 41, 867-875.
15. Walton, M. I.; Smith, P. J.; Workman, P. The Role of NAD(P)H: Quinone Reductase (EC 1.6.99.2, DT-Diaphorase) in the Reductive Bioactivation of Novel Indoloquinone Antitumour Agent EO9. Cancer Commun. 1991, 3, 199-206.
16. Beall, H. D.; Mulcahy, T.; Siegel, D.; Traver, R. D.; Gibson, N. W.; Ross, D. Metabolism of Bioreductive Antitumour Compounds by Purified Rat and Human DT Diaphorases. Cancer Res. 1994, 54, 3196-3201.
17. Chen, S.; Knox, R.; Wu, K.; Deng, P. S.-K.; Zhou, D.; Bianchet, M. A.; Amzel, L. M. Molecular Basis of the Catalytic Differences among DT-Diaphorase of Human, Rat, and Mouse. J. Biol. Chem. 1997, 272, 1437-1439.
18. Chen, S.; Hwang, J.; Deng, P. S.-K. Inhibition of NAD(P)H: Quinone Acceptor Oxidoreductase by Flavones: a Structure -Activity Study. Arch. Biochem. Biophys. 1993, 302, 72-77.
19. Knox, R. J.; Boland, M. P.; Friedlos, F.; Coles, B.; Southan, C.; Roberts, J. J. The Nitroreductase Enzyme in Walker Cells that Activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nittrobenzamide is a Form of NAD(P)H Dehydrogenase (Quinone) (EC 1.6.99.2). Biochem. Pharmacol. 1988, 37, 4671-4677.
20. Matthews, B. W. Solvent Content of Protein Crystals. J. Mol. Biol. 1968, 33, 491-497.
21. Navaza, J. AmoRe: an Automated Package for Molecular Replacement. Acta Crystallogr. 1994, A50, 795-800.
22. Otwinowski, Z. Data Collection and Processing. In Proceedings of the CCP4 Study Weekend; Sawyer, L., Isaacs, N., Bailey, S., Eds.; 1993.
23. Brünger, A. T. XPLOR Version 3.1; Yale University Press: New Haven, CT, 1993.
24. Jones, T. A.; Zou, J.-Y.; Cowan, S. W.; Kjeldgaard, M. Improved Methods for the Building of Protein Models in Electron Density Maps and the Location of Errors in these Models. Acta Crystallogr. 1991, A47, 110-119.
25. Iball, J.; Scrimgour, S. N.; Williams, B. C. The Crystal and Molecular Structure of 2,4-dinitro-5-ethyleneiminobenzamide. Acta Crystallogr. 1975, B31, 1121-1123.
26. Luty, B. A.; Wasserman, Z. R.; Stouten, P. F. W.; Hodge, C. N.; Zacharias, M.; McCammon, J. A. A Molecular Mechanics/Grid Method for Evaluation of Ligand - Receptor Interactions. J. Comput. Chem. 1995, 16, 454-464.
27. Dauber-Osguthorpe, P.; Roberts, V. A.; Osguthorpe, D. J.; Wolff, J.; Genest, M.; Hagler, A. T. Structure and Energetics of Ligand Binding to Proteins: E. coli Dihydrofolate Reductase-trimethoprim, a Drug-receptor System. Proteins 1988, 4, 31-47.