|Gene:||yieF||Accession Numbers: EG11723 (MetaCyc), b3713, ECK3706|
Species: Escherichia coli K-12 substr. MG1655
YieF is a flavoprotein containing the FMN cofactor [Ackerley04]. The enzyme is able to reduce chromate in vitro. Evidence is consistent with the model of an obligatory four-electron reduction of chromate, where the enzyme transfers three electrons to Cr(VI), producing Cr(III), and one electron to molecular oxygen or an oxygen equivalent - without producing the toxic Cr(V) species and only producing the minimal amount of reactive oxygen species (ROS) [Ackerley04]. Chromate reductase may be inhibited by certain divalent cations [Ackerley04].
Chromate (VI) is primarily an anthropogenic environmental contaminant, and thus it is unlikely that YieF has evolved specifically for Cr(VI) detoxification. YieF was shown to possess quinone reductase activity which may guard against oxidative stress by preventing redox cycling of quinones which would otherwise generate ROS and by maintaining a pool of reduced quinone in the cell that is able to quench ROS directly ([Ackerley04] and Ackerley et al, unpublished). The quinone reductase activity of YieF is likely the primary biological role of this enzyme [Ackerley04a].
Expression of yieF is induced in stationary phase and by the presence of chromate [Ackerley04]. Overexpression of YieF results in a two-fold increase in chromate reduction without affecting growth [Ackerley04a] and increases hydrogen peroxide tolerance and scavenging (Ackerley et al, unpublished). A yieF mutant has increased sensitivity to chromate [Ackerley06].
An evolved derivative of YieF with improved chromate reductase activity is being investigated as a prodrug-activating enzyme in cancer chemotherapy [Barak06a].
|Map Position: [3,892,675 -> 3,893,241]|
Molecular Weight of Polypeptide: 20.376 kD (from nucleotide sequence), 22 kD (experimental) [Ackerley04 ]
Molecular Weight of Multimer: 50 kD (experimental) [Ackerley04]
Unification Links: ASAP:ABE-0012146 , DIP:DIP-36041N , EchoBASE:EB1674 , EcoGene:EG11723 , EcoliWiki:b3713 , ModBase:P0AGE6 , OU-Microarray:b3713 , PortEco:yieF , Pride:P0AGE6 , Protein Model Portal:P0AGE6 , RefSeq:NP_418169 , RegulonDB:EG11723 , SMR:P0AGE6 , String:511145.b3713 , Swiss-Model:P0AGE6 , UniProt:P0AGE6
Instance reactions of [an electron-transfer quinone[inner membrane] + NAD(P)H + H+ → an electron-transfer quinol[inner membrane] + NAD(P)+] (22.214.171.124):
|Biological Process:||GO:0006805 - xenobiotic metabolic process
GO:0055114 - oxidation-reduction process [UniProtGOA11a]
|Molecular Function:||GO:0010181 - FMN binding
GO:0016491 - oxidoreductase activity [UniProtGOA11a, GOA01a, Ackerley04]
GO:0003955 - NAD(P)H dehydrogenase (quinone) activity [GOA01]
|Cellular Component:||GO:0005829 - cytosol [DiazMejia09, Ishihama08]|
|MultiFun Terms:||cell processes → protection → detoxification|
Enzymatic reaction of: quinone reductase (chromate reductase)
EC Number: 126.96.36.199
Enzymatic reaction of: chromate reductase
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is physiologically favored in the direction shown.
Note: The enzyme may catalyze this reaction in vitro, but this reaction is not considered to be physiologically relevant.
T(opt): 35 °C [Ackerley04]
pH(opt): 5.0 [Ackerley04]
|Feature Class||Location||Attached Group||Citations||Comment|
|Nucleotide-Phosphate-Binding-Region||13 -> 20||FMN|
|Nucleotide-Phosphate-Binding-Region||82 -> 85||FMN|
Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01 ].
1/26/1998 (pkarp) Merged genes G7792/b3713 and EG11723/yieF
Ackerley04: Ackerley DF, Gonzalez CF, Park CH, Blake R, Keyhan M, Matin A (2004). "Chromate-reducing properties of soluble flavoproteins from Pseudomonas putida and Escherichia coli." Appl Environ Microbiol 70(2);873-82. PMID: 14766567
Ackerley04a: Ackerley DF, Gonzalez CF, Keyhan M, Blake R, Matin A (2004). "Mechanism of chromate reduction by the Escherichia coli protein, NfsA, and the role of different chromate reductases in minimizing oxidative stress during chromate reduction." Environ Microbiol 6(8);851-60. PMID: 15250887
Barak06a: Barak Y, Thorne SH, Ackerley DF, Lynch SV, Contag CH, Matin A (2006). "New enzyme for reductive cancer chemotherapy, YieF, and its improvement by directed evolution." Mol Cancer Ther 5(1);97-103. PMID: 16432167
Barak06b: Barak Y, Ackerley DF, Dodge CJ, Banwari L, Alex C, Francis AJ, Matin A (2006). "Analysis of novel soluble chromate and uranyl reductases and generation of an improved enzyme by directed evolution." Appl Environ Microbiol 72(11);7074-82. PMID: 17088379
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Eswaramoorthy12: Eswaramoorthy S, Poulain S, Hienerwadel R, Bremond N, Sylvester MD, Zhang YB, Berthomieu C, Van Der Lelie D, Matin A (2012). "Crystal structure of ChrR--a quinone reductase with the capacity to reduce chromate." PLoS One 7(4);e36017. PMID: 22558308
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