3H96

Msmeg_3358 F420 Reductase

Summary for 3H96

• Entry DOI: 10.2210/pdb3h96/pdb
• Descriptor: F420-H2 Dependent Reductase A, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: pnpox, f420, flavin, reductase, aflatoxin, flavoprotein
• Biological source: Mycobacterium smegmatis str. MC2 155
• Total number of polymer chains: 4
• Total formula weight: 62625.12

Authors

Jackson, C.J.,French, N.,Newman, J.,Taylor, M.C.,Russell, R.J.,Oakeshott, J.G. (deposition date: 2009-04-30, release date: 2010-04-14, Last modification date: 2024-11-06)

Primary citation

Taylor, M.C.,Jackson, C.J.,Tattersall, D.B.,French, N.,Peat, T.S.,Newman, J.,Briggs, L.J.,Lapalikar, G.V.,Campbell, P.M.,Scott, C.,Russell, R.J.,Oakeshott, J.G.
Identification and characterization of two families of F420 H2-dependent reductases from Mycobacteria that catalyse aflatoxin degradation.
Mol.Microbiol., 78:561-575, 2010

PubMed Abstract: Aflatoxins are polyaromatic mycotoxins that contaminate a range of food crops as a result of fungal growth and contribute to serious health problems in the developing world because of their toxicity and mutagenicity. Although relatively resistant to biotic degradation, aflatoxins can be metabolized by certain species of Actinomycetales. However, the enzymatic basis for their breakdown has not been reported until now. We have identified nine Mycobacterium smegmatis enzymes that utilize the deazaflavin cofactor F(420) H(2) to catalyse the reduction of the α,β-unsaturated ester moiety of aflatoxins, activating the molecules for spontaneous hydrolysis and detoxification. These enzymes belong to two previously uncharacterized F(420) H(2) dependent reductase (FDR-A and -B) families that are distantly related to the flavin mononucleotide (FMN) dependent pyridoxamine 5'-phosphate oxidases (PNPOxs). We have solved crystal structures of an enzyme from each FDR family and show that they, like the PNPOxs, adopt a split barrel protein fold, although the FDRs also possess an extended and highly charged F(420) H(2) binding groove. A general role for these enzymes in xenobiotic metabolism is discussed, including the observation that the nitro-reductase Rv3547 from Mycobacterium tuberculosis that is responsible for the activation of bicyclic nitroimidazole prodrugs belongs to the FDR-A family.

PubMed: 20807200
DOI: 10.1111/j.1365-2958.2010.07356.x

Experimental method

X-RAY DIFFRACTION (2 Å)