Escherichia coli K-12 substr. MG1655 Enzyme: arsenate reductase

Gene: arsC Accession Numbers: EG12237 (EcoCyc), b3503, ECK3488

Synonyms: arsG

Regulation Summary Diagram: ?

Regulation summary diagram for arsC

Based on sequence similarity with the R773-encoded enzyme, ArsC is thought to catalyze the reduction of arsenate to arsenite using glutathione with glutaredoxin as electron donors. The resulting arsenite is then removed from the cell via the ArsB transport protein.

Unlike the chromosomally-encoded ArsC described here, the R773 plasmid-encoded enzyme has been studied experimentally. The arsenate reductase reaction involves sequential action of three different thiolate nucleophiles that function as a redox cascade [Messens06]. All three glutaredoxins in E. coli can participate in the arsenate reductase reaction, but glutaredoxin 2 appears the most effective [Shi99a]. Crystal structures of ArsC have been solved [Martin01a, DeMel04], and residues involved in arsenate binding and transition-state stabilization were identified [Shi03, DeMel04].

Based on sequence similarity with the R773-plasmid encoded arsenite resistance operon, ArsB is a transporter and ArsC is an arsenate reductase [Diorio95, Carlin95]. The chromosomally encoded operon, however, is lacking arsA, which encodes a putative ATP-binding protein.

Expression of arsRBC is induced by exposure to arsenite [Diorio95, Carlin95]; transcription is negatively regulated by ArsR [Cai96]. arsRBC mutants are more sensitive to sodium arsenate and arsenite than wild type, while overexpression of arsRBC from a plasmid leads to increased arsenate, arsenite and antimonite resistance [Diorio95, Carlin95]. ΔarsRBC mutant accumulates significantly more intracellular arsenite than wild type [Carlin95].

Reviews: [Mukhopadhyay02, Rosen02, Messens06]

Citations: [Kaur09, Chaturvedi14]

Locations: cytosol

Map Position: [3,648,260 -> 3,648,685] (78.63 centisomes, 283°)
Length: 426 bp / 141 aa

Molecular Weight of Polypeptide: 15.853 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0011439 , CGSC:35999 , EchoBASE:EB2149 , EcoGene:EG12237 , EcoliWiki:b3503 , ModBase:P0AB96 , OU-Microarray:b3503 , PortEco:arsC , PR:PRO_000022155 , Pride:P0AB96 , Protein Model Portal:P0AB96 , RefSeq:NP_417960 , RegulonDB:EG12237 , SMR:P0AB96 , String:511145.b3503 , Swiss-Model:P0AB96 , UniProt:P0AB96

Relationship Links: InterPro:IN-FAMILY:IPR006659 , InterPro:IN-FAMILY:IPR006660 , InterPro:IN-FAMILY:IPR012336 , PDB:Homolog:1I9D , Pfam:IN-FAMILY:PF03960 , Prosite:IN-FAMILY:PS51353

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for arsC

GO Terms:

Biological Process: GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
GO:0046685 - response to arsenic-containing substance Inferred from experiment Inferred by computational analysis [UniProtGOA11, Carlin95, Diorio95]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0008794 - arsenate reductase (glutaredoxin) activity Inferred by computational analysis [GOA01a, GOA01, Carlin95]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: cell processes protection detoxification

Essentiality data for arsC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Last-Curated ? 13-Oct-2014 by Keseler I , SRI International

Enzymatic reaction of: arsenate reductase

Synonyms: arsenical pump modifier

EC Number:

arsenate + a reduced glutaredoxin + H+ <=> arsenite + an oxidized glutaredoxin + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.

In Pathways: arsenate detoxification II (glutaredoxin)

Kinetic Parameters:

Km (μM)

pH(opt): 6.3

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b3503 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12237; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Cai96: Cai J, DuBow MS (1996). "Expression of the Escherichia coli chromosomal ars operon." Can J Microbiol 1996;42(7);662-71. PMID: 8764681

Carlin95: Carlin A, Shi W, Dey S, Rosen BP (1995). "The ars operon of Escherichia coli confers arsenical and antimonial resistance." J Bacteriol 1995;177(4);981-6. PMID: 7860609

Chaturvedi14: Chaturvedi N, Pandey PN (2014). "Phylogenetic analysis of gammaproteobacterial arsenate reductase proteins specific to Enterobacteriaceae family, signifying arsenic toxicity." Interdiscip Sci 6(1);57-62. PMID: 24464705

DeMel04: DeMel S, Shi J, Martin P, Rosen BP, Edwards BF (2004). "Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773 determines the chemical nature of the bound As(III) product." Protein Sci 13(9);2330-40. PMID: 15295115

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

Diorio95: Diorio C, Cai J, Marmor J, Shinder R, DuBow MS (1995). "An Escherichia coli chromosomal ars operon homolog is functional in arsenic detoxification and is conserved in gram-negative bacteria." J Bacteriol 1995;177(8);2050-6. PMID: 7721697

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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.

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kaur09: Kaur S, Kamli MR, Ali A (2009). "Diversity of arsenate reductase genes (arsC Genes) from arsenic-resistant environmental isolates of E. coli." Curr Microbiol 59(3);288-94. PMID: 19484295

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Martin01a: Martin P, DeMel S, Shi J, Gladysheva T, Gatti DL, Rosen BP, Edwards BF (2001). "Insights into the structure, solvation, and mechanism of ArsC arsenate reductase, a novel arsenic detoxification enzyme." Structure 9(11);1071-81. PMID: 11709171

Messens06: Messens J, Silver S (2006). "Arsenate reduction: thiol cascade chemistry with convergent evolution." J Mol Biol 362(1);1-17. PMID: 16905151

Mukhopadhyay02: Mukhopadhyay R, Rosen BP (2002). "Arsenate reductases in prokaryotes and eukaryotes." Environ Health Perspect 110 Suppl 5;745-8. PMID: 12426124

Rosen02: Rosen BP (2002). "Transport and detoxification systems for transition metals, heavy metals and metalloids in eukaryotic and prokaryotic microbes." Comp Biochem Physiol A Mol Integr Physiol 133(3);689-93. PMID: 12443926

Shi03: Shi J, Mukhopadhyay R, Rosen BP (2003). "Identification of a triad of arginine residues in the active site of the ArsC arsenate reductase of plasmid R773." FEMS Microbiol Lett 227(2);295-301. PMID: 14592722

Shi99a: Shi J, Vlamis-Gardikas A, Aslund F, Holmgren A, Rosen BP (1999). "Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli shows that glutaredoxin 2 is the primary hydrogen donor to ArsC-catalyzed arsenate reduction." J Biol Chem 1999;274(51);36039-42. PMID: 10593884

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

Other References Related to Gene Regulation

Busenlehner03: Busenlehner LS, Pennella MA, Giedroc DP (2003). "The SmtB/ArsR family of metalloregulatory transcriptional repressors: Structural insights into prokaryotic metal resistance." FEMS Microbiol Rev 27(2-3);131-43. PMID: 12829264

Xu96b: Xu C, Shi W, Rosen BP (1996). "The chromosomal arsR gene of Escherichia coli encodes a trans-acting metalloregulatory protein." J Biol Chem 1996;271(5);2427-32. PMID: 8576202

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Thu Oct 8, 2015, biocyc12.