1DXO

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 1DXO

• Entry DOI: 10.2210/pdb1dxo/pdb
• Descriptor: QUINONE REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE, DUROQUINONE, ... (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: 126904.65

Authors

Faig, M.,Bianchet, M.A.,Chen, S.,Winski, S.,Ross, D.,Amzel, L.M. (deposition date: 2000-01-12, release date: 2000-04-23, Last modification date: 2024-05-08)

Primary citation

Faig, M.,Bianchet, M.A.,Chen, S.,Winski, S.,Ross, D.,Talalay, P.,Amzel, L.M.
Structures of Recombinant Mouse and Human Nad(P)H:Quinone Oxidoreductases:Species Comparison and Structural Changes with Substrate Binding and Release
Proc.Natl.Acad.Sci.USA, 97:3177-, 2000

PubMed Abstract: NAD(P)H/quinone acceptor oxidoreductase (QR1, NQO1, formerly DT-diaphorase; EC ) protects animal cells from the deleterious and carcinogenic effects of quinones and other electrophiles. In this paper we report the apoenzyme structures of human (at 1.7-A resolution) and mouse (2.8 A) QR1 and the complex of the human enzyme with the substrate duroquinone (2.5 A) (2,3,5, 6-tetramethyl-p-benzoquinone). In addition to providing a description and rationale of the structural and catalytic differences among several species, these structures reveal the changes that accompany substrate or cofactor (NAD) binding and release. Tyrosine-128 and the loop spanning residues 232-236 close the binding site, partially occupying the space left vacant by the departing molecule (substrate or cofactor). These changes highlight the exquisite control of access to the catalytic site that is required by the ping-pong mechanism in which, after reducing the flavin, NAD(P)(+) leaves the catalytic site and allows substrate to bind at the vacated position. In the human QR1-duroquinone structure one ring carbon is significantly closer to the flavin N5, suggesting a direct hydride transfer to this atom.

PubMed: 10706635
DOI: 10.1073/PNAS.050585797

Experimental method

X-RAY DIFFRACTION (2.5 Å)