3R6W

paAzoR1 binding to nitrofurazone

Summary for 3R6W

• Entry DOI: 10.2210/pdb3r6w/pdb
• Related: 2V9C 3KEG 3LT5
• Descriptor: FMN-dependent NADH-azoreductase 1, FLAVIN MONONUCLEOTIDE, NITROFURAZONE, ... (6 entities in total)
• Functional Keywords: azoreductase, nitrofurazone, p. aeruginosa, nitroreductase, short-flavodoxin, oxidoreductase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 48203.83

Authors

Ryan, A.,Kaplan, K.,Laurieri, N.,Lowe, E.,Sim, E. (deposition date: 2011-03-22, release date: 2011-08-24, Last modification date: 2023-09-13)

Primary citation

Ryan, A.,Kaplan, E.,Laurieri, N.,Lowe, E.,Sim, E.
Activation of nitrofurazone by azoreductases: multiple activities in one enzyme.
Sci Rep, 1:63-63, 2011

PubMed 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.

PubMed: 22355582
DOI: 10.1038/srep00063

Experimental method

X-RAY DIFFRACTION (2.085 Å)