1H69

CRYSTAL STRUCTURE OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE CO WITH 2,3,5,6,TETRAMETHYL-P-BENZOQUINONE (DUROQUINONE) AT 2.5 ANGSTROM RESOLUTION

Summary for 1H69

• Entry DOI: 10.2210/pdb1h69/pdb
• Related: 1D4A 1DXO 1H66 1QBG
• Descriptor: NAD(P)H DEHYDROGENASE [QUINONE] 1, FLAVIN-ADENINE DINUCLEOTIDE, 3-(HYDROXYMETHYL)-1-METHYL-5-(2-METHYLAZIRIDIN-1-YL)-2-PHENYL-1H-INDOLE-4,7-DIONE, ... (4 entities in total)
• Functional Keywords: flavoprotein, rossmann fold, oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P15559
• Total number of polymer chains: 4
• Total formula weight: 127425.08

Authors

Faig, M.,Bianchet, M.A.,Chen, S.,Winski, S.,Ross, D.,Amzel, L.M. (deposition date: 2001-06-08, release date: 2001-09-05, Last modification date: 2023-12-13)

Primary citation

Faig, M.,Bianchet, M.A.,Winski, S.,Hargreaves, R.,Moody, C.J.,Hudnott, A.R.,Ross, D.,Amzel, L.M.
Structure-Based Development of Anticancer Drugs: Complexes of Nad(P)H:Quinone Oxidoreductase 1 with Chemotherapeutic Quinones
Structure, 9:659-, 2001

PubMed Abstract: NAD(P)H:quinone acceptor oxidoreductase (QR1) protects animal cells from the deleterious and carcinogenic effects of quinones and other electrophiles. Remarkably, the same enzyme activates cancer prodrugs that become cytotoxic only after two-electron reduction. QR1's ability to bioactivate quinones and its elevated expression in many human solid tumors makes this protein an excellent target for enzyme-directed drug development. Until now, structural analysis of the mode of binding of chemotherapeutic compounds to QR1 was based on model building using the structures of complexes with simple substrates; no structure of complexes of QR1 with chemotherapeutic prodrugs had been reported.

PubMed: 11587640
DOI: 10.1016/S0969-2126(01)00636-0

Experimental method

X-RAY DIFFRACTION (1.86 Å)