Journal of Biological Chemistry
Volume 277, Issue 13, 29 March 2002, Pages 11513-11520
Journal home page for Journal of Biological Chemistry

ENZYME CATALYSIS AND REGULATION
Structures of Nitroreductase in Three States: EFFECTS OF INHIBITOR BINDING AND REDUCTION*

https://doi.org/10.1074/jbc.M111334200Get rights and content
Under a Creative Commons license
open access

The crystal structure of the nitroreductase enzyme from Enterobacter cloacae has been determined for the oxidized form in separate complexes with benzoate and acetate inhibitors and for the two-electron reduced form. Nitroreductase is a member of a group of enzymes that reduce a broad range of nitroaromatic compounds and has potential uses in chemotherapy and bioremediation. The monomers of the nitroreductase dimer adopt an α+β fold and together bind two flavin mononucleotide prosthetic groups at the dimer interface. In the oxidized enzyme, the flavin ring system adopts a strongly bent (16°) conformation, and the bend increases (25°) in the reduced form of the enzyme, roughly the conformation predicted for reduced flavin free in solution. Because free oxidized flavin is planar, the induced bend in the oxidized enzyme may favor reduction, and it may also account for the characteristic inability of the enzyme to stabilize the one electron-reduced semiquinone flavin, which is also planar. Both inhibitors bind over the pyrimidine and central rings of the flavin in partially overlapping sites. Comparison of the two inhibitor complexes shows that a portion of helix H6 can flex to accommodate the differently sized inhibitors suggesting a mechanism for accommodating varied substrates.

Cited by (0)

Published, JBC Papers in Press, January 22, 2002, DOI 10.1074/jbc.M111334200

*

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and the structure factors (code,, ) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

Present address: The Johnson Foundation, Dept. of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.