1QBG

CRYSTAL STRUCTURE OF HUMAN DT-DIAPHORASE (NAD(P)H OXIDOREDUCTASE)

Summary for 1QBG

• Entry DOI: 10.2210/pdb1qbg/pdb
• Descriptor: NAD(P)H DEHYDROGENASE [QUINONE] 1, FLAVIN-ADENINE DINUCLEOTIDE (2 entities in total)
• Functional Keywords: quinone, fad, oxidoreductase, dt-diaphorase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15559
• Total number of polymer chains: 4
• Total formula weight: 126019.66

Authors

Skelly, J.V.,Sanderson, M.R.,Suter, D.A.,Baumann, U.,Gregory, D.S.,Bennett, M.,Hobbs, S.M.,Neidle, S. (deposition date: 1999-04-20, release date: 2000-04-24, Last modification date: 2024-02-14)

Primary citation

Skelly, J.V.,Sanderson, M.R.,Suter, D.A.,Baumann, U.,Read, M.A.,Gregory, D.S.,Bennett, M.,Hobbs, S.M.,Neidle, S.
Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954).
J.Med.Chem., 42:4325-4330, 1999

PubMed Abstract: The crystal structure of human DT-diaphorase (NAD(P)H oxidoreductase (quinone); EC 1.6.99.2) has been determined to 2.3 A resolution. There are only minor differences in shape and volume between the active sites of the rat and human enzymes and in the hydrophobic environment in the vicinity of the substrate. The isoalloxazine ring of the bound FAD is more buried in the human structure. Molecular modeling was used to examine optimal positions for the antitumor prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) in both the human and rat enzyme active sites. This suggests that the position of CB1954 in the active site of the human enzyme is very similar to that in the rat, although there are detailed differences in the predicted patterns of hydrogen bonding between side chains and the drug. Some of the differences are a consequence of the shift in position for the FAD molecule and may contribute to the observed differences in rate of the two-electron reduction of CB1954.

PubMed: 10543876
DOI: 10.1021/jm991060m

Experimental method

X-RAY DIFFRACTION (2.3 Å)