MetaCyc Enzyme: chromate reductase

Gene: yieF Accession Numbers: EG11723 (MetaCyc), b3713, ECK3706

Synonyms: chrR

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of chromate reductase = [YieF]2
         chromate reductase monomer = YieF

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maintaining a pool of reduced quinone in the cell that is able to quench ROS directly ([Ackerley04] and Ackerley et al, unpublished).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without affecting growth [Ackerley04a] and increases hydrogen peroxide tolerance and scavenging (Ackerley et al, unpublished).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].

Locations: cytosol

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

Relationship Links: InterPro:IN-FAMILY:IPR005025 , InterPro:IN-FAMILY:IPR029039 , PDB:Structure:3SVL , Pfam:IN-FAMILY:PF03358

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Instance reactions of [an electron-transfer quinone[inner membrane] + NAD(P)H + H+ → an electron-transfer quinol[inner membrane] + NAD(P)+] (
i1: NADH[in] + a ubiquinone[membrane] + H+[in] → NAD+[in] + an ubiquinol[membrane] (

i2: NADH[in] + a menaquinone[membrane] + H+[in] → NAD+[in] + a menaquinol[membrane] (no EC#)

GO Terms:

Biological Process: GO:0006805 - xenobiotic metabolic process Inferred from experiment [Ackerley06]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0010181 - FMN binding Inferred from experiment [Ackerley04]
GO:0016491 - oxidoreductase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Ackerley04]
GO:0003955 - NAD(P)H dehydrogenase (quinone) activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: cell processes protection detoxification

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Enzymatic reaction of: quinone reductase (chromate reductase)

EC Number:

Transport reaction diagram for quinone reductase

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Enzymatic reaction of: chromate reductase

Cr6+ + 2 NAD(P)H + oxygen <=> Cr3+ + superoxide + 2 NAD(P)+ + 2 H+

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.

Alternative Substrates for Cr6+: Mo6+ [Ackerley04 ] , V5+ [Ackerley04 ]

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Cofactors or Prosthetic Groups: FMN [Ackerley04]

T(opt): 35 °C [Ackerley04]

pH(opt): 5.0 [Ackerley04]

Sequence Features

Feature Class Location Attached Group Citations Comment
Nucleotide-Phosphate-Binding-Region 13 -> 20 FMN
[Eswaramoorthy12, UniProt14]
UniProt: FMN.
Nucleotide-Phosphate-Binding-Region 82 -> 85 FMN
[Eswaramoorthy12, UniProt14]
UniProt: FMN.
Mutagenesis-Variant 85  
[Eswaramoorthy12, UniProt14]
UniProt: Improves chromate reductase activity compared to the wild-type enzyme.
Amino-Acid-Sites-That-Bind 117  
[Eswaramoorthy12, UniProt14]
UniProt: FMN.
Mutagenesis-Variant 125  
[Eswaramoorthy12, UniProt14]
UniProt: Improves chromate reductase activity compared to the wild-type enzyme.
Mutagenesis-Variant 128  
[Barak06b, UniProt14]
UniProt: Improves chromate reductase activity compared to the wild-type enzyme. Increase of the affinity binding and catalytic efficiency for both chromate and uranate.
Mutagenesis-Variant 146  
[Eswaramoorthy12, UniProt14]
UniProt: Improves chromate reductase activity compared to the wild-type enzyme.

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

Ackerley06: Ackerley DF, Barak Y, Lynch SV, Curtin J, Matin A (2006). "Effect of chromate stress on Escherichia coli K-12." J Bacteriol 188(9);3371-81. PMID: 16621832

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

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Serres01: Serres MH, Gopal S, Nahum LA, Liang P, Gaasterland T, Riley M (2001). "A functional update of the Escherichia coli K-12 genome." Genome Biol 2(9);RESEARCH0035. PMID: 11574054

UniProt14: UniProt Consortium (2014). "UniProt version 2014-08 released on 2014-08-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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