Activation of nitrofurazone by azoreductases: multiple activities in one enzyme

DOI: 10.1038/srep00063
PMID: 22355582

Authors: Ali Ryan (University of Oxford; Kingston University) , Elise Kaplan (University of Oxford) , Nicola Laurieri (University of Oxford) , Ed Lowe (University of Oxford) , Edith Sim (University of Oxford; Kingston University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 1

State: Published (Approved)
Published: August 2011

Abstract: Azoreductases are well known for azo pro-drug activation by gut flora. We show that azoreductases have a wider role in drug metabolism than previously thought as they can also reduce and hence activate nitrofurazone. Nitrofurazone, a nitroaromatic drug, is a broad spectrum antibiotic which has until now been considered as activated in bacteria by nitroreductases. The structure of the azoreductase with nitrofurazone bound was solved at 2.08 Å and shows nitrofurazone in an active conformation. Based on the structural information, the kinetics and stoichiometry of nitrofurazone reduction by azoreductase from P. aeruginosa, we propose a mechanism of activation which accounts for the ability of azoreductases to reduce both azo and nitroaromatic drugs. This mode of activation can explain the cytotoxic side-effects of nitrofurazone through human azoreductase homologues.

Journal Keywords: Models; Molecular; NADH; NADPH; Nitrofurazone

Diamond Keywords: Enzymes; Bacteria

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I02-Macromolecular Crystallography

Added On: 17/08/2011 09:11

Documents:
srep00063.pdf

Discipline Tags:

Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)