ARSC1_ECOLX
ID ARSC1_ECOLX Reviewed; 141 AA.
AC P08692;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Arsenate reductase {ECO:0000303|PubMed:8003492};
DE EC=1.20.4.1 {ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:7577935, ECO:0000269|PubMed:8003492};
DE AltName: Full=Arsenical pump modifier;
GN Name=arsC {ECO:0000303|PubMed:3021763};
OS Escherichia coli.
OG Plasmid R773.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC PLASMID=R773;
RX PubMed=3021763; DOI=10.1016/s0021-9258(18)66824-3;
RA Chen C.-M., Misra T.K., Silver S., Rosen B.P.;
RT "Nucleotide sequence of the structural genes for an anion pump. The
RT plasmid-encoded arsenical resistance operon.";
RL J. Biol. Chem. 261:15030-15038(1986).
RN [2]
RP PROTEIN SEQUENCE OF 5-13, AND SUBUNIT.
RC PLASMID=R773;
RX PubMed=1703401; DOI=10.1016/0003-9861(91)90312-7;
RA Rosen B.P., Weigel U., Monticello R.A., Edwards B.P.F.;
RT "Molecular analysis of an anion pump: purification of the ArsC protein.";
RL Arch. Biochem. Biophys. 284:381-385(1991).
RN [3]
RP REVIEW.
RX PubMed=1704144; DOI=10.1016/0923-2508(90)90008-e;
RA Rosen B.P.;
RT "The plasmid-encoded arsenical resistance pump: an anion-translocating
RT ATPase.";
RL Res. Microbiol. 141:336-341(1990).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC PLASMID=R773;
RX PubMed=8003492; DOI=10.1021/bi00189a033;
RA Gladysheva T.B., Oden K.L., Rosen B.P.;
RT "Properties of the arsenate reductase of plasmid R773.";
RL Biochemistry 33:7288-7293(1994).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACTIVE SITE, AND
RP MUTAGENESIS OF CYS-12 AND CYS-106.
RC PLASMID=R773;
RX PubMed=7577935; DOI=10.1021/bi00041a026;
RA Liu J., Gladysheva T.B., Lee L., Rosen B.P.;
RT "Identification of an essential cysteinyl residue in the ArsC arsenate
RT reductase of plasmid R773.";
RL Biochemistry 34:13472-13476(1995).
RN [6]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-8 AND HIS-88.
RC PLASMID=R773;
RX PubMed=8969183; DOI=10.1074/jbc.271.52.33256;
RA Gladysheva T., Liu J., Rosen B.P.;
RT "His-8 lowers the pKa of the essential Cys-12 residue of the ArsC arsenate
RT reductase of plasmid R773.";
RL J. Biol. Chem. 271:33256-33260(1996).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF ARG-60; LYS-61; ARG-94; ARG-107; GLU-127; ASP-128 AND
RP GLU-130.
RC PLASMID=R773;
RX PubMed=14592722; DOI=10.1016/s0378-1097(03)00695-5;
RA Shi J., Mukhopadhyay R., Rosen B.P.;
RT "Identification of a triad of arginine residues in the active site of the
RT ArsC arsenate reductase of plasmid R773.";
RL FEMS Microbiol. Lett. 227:295-301(2003).
RN [8] {ECO:0007744|PDB:1I9D, ECO:0007744|PDB:1J9B, ECO:0007744|PDB:1JZW}
RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) OF APOENZYME AND IN COMPLEXES WITH
RP ARSENATE AND ARSENITE, AND ACTIVE SITE.
RC PLASMID=R773;
RX PubMed=11709171; DOI=10.1016/s0969-2126(01)00672-4;
RA Martin P., DeMel S., Shi J., Gladysheva T., Gatti D.L., Rosen B.P.,
RA Edwards B.F.;
RT "Insights into the structure, solvation, and mechanism of ArsC arsenate
RT reductase, a novel arsenic detoxification enzyme.";
RL Structure 9:1071-1081(2001).
RN [9] {ECO:0007744|PDB:1S3C, ECO:0007744|PDB:1S3D, ECO:0007744|PDB:1SD8, ECO:0007744|PDB:1SD9, ECO:0007744|PDB:1SJZ, ECO:0007744|PDB:1SK0, ECO:0007744|PDB:1SK1, ECO:0007744|PDB:1SK2}
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF MUTANTS SER-12; ALA-60 AND LYS-60
RP IN APO FORM AND IN COMPLEXES WITH ARSENATE AND ARSENITE, REACTION
RP MECHANISM, AND ACTIVE SITE.
RC PLASMID=R773;
RX PubMed=15295115; DOI=10.1110/ps.04787204;
RA DeMel S., Shi J., Martin P., Rosen B.P., Edwards B.F.;
RT "Arginine 60 in the ArsC arsenate reductase of E. coli plasmid R773
RT determines the chemical nature of the bound As(III) product.";
RL Protein Sci. 13:2330-2340(2004).
CC -!- FUNCTION: Involved in resistance to arsenate (PubMed:3021763,
CC PubMed:8003492, PubMed:7577935). Catalyzes the reduction of arsenate
CC [As(V)] to arsenite [As(III)] (PubMed:8003492, PubMed:7577935,
CC PubMed:14592722). The resulting arsenite is then extruded from the cell
CC via the ArsAB transport system (Probable).
CC {ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:3021763,
CC ECO:0000269|PubMed:7577935, ECO:0000269|PubMed:8003492, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[glutaredoxin]-dithiol + arsenate + glutathione + H(+) =
CC arsenite + glutathionyl-S-S-[glutaredoxin] + H2O;
CC Xref=Rhea:RHEA:22016, Rhea:RHEA-COMP:10729, Rhea:RHEA-COMP:17668,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29242,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:48597, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:146199; EC=1.20.4.1;
CC Evidence={ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:7577935,
CC ECO:0000269|PubMed:8003492};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22017;
CC Evidence={ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:7577935,
CC ECO:0000269|PubMed:8003492};
CC -!- ACTIVITY REGULATION: Inhibited by the thiol reagents iodoacetate (IAA)
CC and N-ethylmaleimide (NEM) (PubMed:7577935). Activity is rapidly
CC inactivated by the histidine-modifying reagent diethylpyrocarbonate
CC (DEPC) (PubMed:8969183). {ECO:0000269|PubMed:7577935,
CC ECO:0000269|PubMed:8969183}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 mM for arsenate {ECO:0000269|PubMed:8003492};
CC KM=15.2 mM for arsenate {ECO:0000269|PubMed:14592722};
CC KM=32.9 nM for glutaredoxin Grx2 {ECO:0000269|PubMed:14592722};
CC Note=kcat is 0.53 sec(-1) with arsenate as substrate. kcat is 0.218
CC sec(-1) with Grx2 as substrate. {ECO:0000269|PubMed:14592722};
CC pH dependence:
CC Optimum pH is 6.3-6.8. {ECO:0000269|PubMed:8003492};
CC -!- SUBUNIT: Monomer in solution. {ECO:0000269|PubMed:1703401}.
CC -!- SIMILARITY: Belongs to the ArsC family. {ECO:0000305}.
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DR EMBL; J02591; AAA21096.1; -; Genomic_DNA.
DR PIR; C25937; C25937.
DR RefSeq; WP_011117598.1; NZ_VNXP01000024.1.
DR PDB; 1I9D; X-ray; 1.65 A; A=1-141.
DR PDB; 1J9B; X-ray; 1.26 A; A=1-141.
DR PDB; 1JZW; X-ray; 1.76 A; A=1-140.
DR PDB; 1S3C; X-ray; 1.25 A; A=1-141.
DR PDB; 1S3D; X-ray; 1.54 A; A=3-140.
DR PDB; 1SD8; X-ray; 1.59 A; A=1-141.
DR PDB; 1SD9; X-ray; 1.65 A; A=1-141.
DR PDB; 1SJZ; X-ray; 1.80 A; A=1-140.
DR PDB; 1SK0; X-ray; 1.80 A; A=1-140.
DR PDB; 1SK1; X-ray; 1.55 A; A=1-140.
DR PDB; 1SK2; X-ray; 1.54 A; A=1-140.
DR PDBsum; 1I9D; -.
DR PDBsum; 1J9B; -.
DR PDBsum; 1JZW; -.
DR PDBsum; 1S3C; -.
DR PDBsum; 1S3D; -.
DR PDBsum; 1SD8; -.
DR PDBsum; 1SD9; -.
DR PDBsum; 1SJZ; -.
DR PDBsum; 1SK0; -.
DR PDBsum; 1SK1; -.
DR PDBsum; 1SK2; -.
DR AlphaFoldDB; P08692; -.
DR SMR; P08692; -.
DR STRING; 585034.ECIAI1_3650; -.
DR DrugBank; DB04456; Arsenous acid.
DR DrugBank; DB03352; S-Arsonocysteine.
DR DrugBank; DB03289; Thiarsa Dihydroxy Cysteine.
DR DrugBank; DB01808; Thiarsahydroxy-Cysteine.
DR eggNOG; COG1393; Bacteria.
DR BioCyc; MetaCyc:MON-21672; -.
DR EvolutionaryTrace; P08692; -.
DR GO; GO:0008794; F:arsenate reductase (glutaredoxin) activity; IEA:UniProtKB-EC.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEA:UniProtKB-KW.
DR CDD; cd03034; ArsC_ArsC; 1.
DR InterPro; IPR006659; Arsenate_reductase.
DR InterPro; IPR006660; Arsenate_reductase-like.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR30041; PTHR30041; 1.
DR Pfam; PF03960; ArsC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR00014; arsC; 1.
DR PROSITE; PS51353; ARSC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Arsenical resistance; Direct protein sequencing;
KW Oxidoreductase; Plasmid.
FT CHAIN 1..141
FT /note="Arsenate reductase"
FT /id="PRO_0000162537"
FT ACT_SITE 12
FT /note="Nucleophile; cysteine thioarsenate intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01282,
FT ECO:0000269|PubMed:11709171, ECO:0000269|PubMed:15295115,
FT ECO:0000269|PubMed:7577935"
FT SITE 8
FT /note="Important for activity. Lowers pKa of the active
FT site Cys"
FT /evidence="ECO:0000269|PubMed:8969183"
FT SITE 60
FT /note="Important for activity. Involved in arsenate binding
FT and transition-state stabilization"
FT /evidence="ECO:0000269|PubMed:11709171,
FT ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:15295115"
FT SITE 94
FT /note="Important for activity. Involved in arsenate binding
FT and transition-state stabilization"
FT /evidence="ECO:0000269|PubMed:11709171,
FT ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:15295115"
FT SITE 107
FT /note="Important for activity. Involved in arsenate binding
FT and transition-state stabilization"
FT /evidence="ECO:0000269|PubMed:11709171,
FT ECO:0000269|PubMed:14592722, ECO:0000269|PubMed:15295115"
FT MUTAGEN 8
FT /note="H->P,G,R: Loss of reductase activity. Mutant is
FT sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:8969183"
FT MUTAGEN 8
FT /note="H->S: Mutant is sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:8969183"
FT MUTAGEN 12
FT /note="C->A,G: Mutant is sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:7577935"
FT MUTAGEN 12
FT /note="C->S: Loss of reductase activity. Mutant is
FT sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:7577935"
FT MUTAGEN 60
FT /note="R->A: 50-fold decrease in catalytic efficiency with
FT arsenate. Mutant is sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 60
FT /note="R->E: 70-fold decrease in catalytic efficiency with
FT arsenate. Mutant is sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 60
FT /note="R->K: 22-fold decrease in catalytic efficiency with
FT arsenate. Mutant shows low-level resistance to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 61
FT /note="K->A,E,R: Mutant retains arsenate resistance."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 88
FT /note="H->R,S,V,W: No change in reductase activity. Mutant
FT retains arsenate resistance."
FT /evidence="ECO:0000269|PubMed:8969183"
FT MUTAGEN 94
FT /note="R->A,E,Y: Loss of reductase activity. Mutant is
FT sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 94
FT /note="R->K: Loss of reductase activity. Mutant exhibits
FT slight resistance to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 106
FT /note="C->G,S: Retains reductase activity. Mutant retains
FT arsenate resistance."
FT /evidence="ECO:0000269|PubMed:7577935"
FT MUTAGEN 106
FT /note="C->V: Mutant retains arsenate resistance."
FT /evidence="ECO:0000269|PubMed:7577935"
FT MUTAGEN 107
FT /note="R->A,E,Y: Loss of reductase activity. Mutant is
FT sensitive to arsenate."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 107
FT /note="R->K: Mutant retains arsenate resistance."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 127
FT /note="E->A: 6-fold decrease in catalytic efficiency with
FT arsenate. Mutant is sensitive at high arsenate
FT concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 127
FT /note="E->D: 13-fold decrease in catalytic efficiency with
FT arsenate. Mutant is sensitive at high arsenate
FT concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 127
FT /note="E->K: 17-fold decrease in catalytic efficiency with
FT arsenate. Mutant is sensitive at high arsenate
FT concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 128
FT /note="D->A: 4-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 128
FT /note="D->E: 7-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 128
FT /note="D->K: 9-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 130
FT /note="E->A: 3-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 130
FT /note="E->D: 5-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT MUTAGEN 130
FT /note="E->K: 5-fold decrease in catalytic efficiency with
FT arsenate. Mutant is relatively resistant to arsenate, but
FT is more sensitive at higher concentrations."
FT /evidence="ECO:0000269|PubMed:14592722"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 13..24
FT /evidence="ECO:0007829|PDB:1S3C"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:1S3C"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:1S3C"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 64..68
FT /evidence="ECO:0007829|PDB:1S3C"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 78..87
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:1S3C"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:1S3C"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:1S3C"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:1S3C"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1S3C"
SQ SEQUENCE 141 AA; 15830 MW; 240F4105487E2FBF CRC64;
MSNITIYHNP ACGTSRNTLE MIRNSGTEPT IILYLENPPS RDELVKLIAD MGISVRALLR
KNVEPYEQLG LAEDKFTDDQ LIDFMLQHPI LINRPIVVTP LGTRLCRPSE VVLDILQDAQ
KGAFTKEDGE KVVDEAGKRL K
