FOSA_SERMA
ID FOSA_SERMA Reviewed; 141 AA.
AC Q56415;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Glutathione transferase FosA;
DE EC=2.5.1.18;
DE AltName: Full=Fosfomycin resistance protein;
GN Name=fosA; Synonyms=fos;
OS Serratia marcescens.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Yersiniaceae; Serratia.
OX NCBI_TaxID=615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RC TRANSPOSON=Tn2921;
RX PubMed=1963292; DOI=10.1128/aac.34.10.2016;
RA Navas J., Leon J., Arroyo M., Garcia Lobo J.M.;
RT "Nucleotide sequence and intracellular location of the product of the
RT fosfomycin resistance gene from transposon Tn2921.";
RL Antimicrob. Agents Chemother. 34:2016-2018(1990).
RN [2]
RP FUNCTION, COFACTOR, AND SUBUNIT.
RX PubMed=9115979; DOI=10.1021/bi963172a;
RA Bernat B.A., Laughlin L.T., Armstrong R.N.;
RT "Fosfomycin resistance protein (FosA) is a manganese metalloglutathione
RT transferase related to glyoxalase I and the extradiol dioxygenases.";
RL Biochemistry 36:3050-3055(1997).
RN [3]
RP METAL-BINDING SITES, AND MUTAGENESIS OF HIS-7; HIS-67 AND GLU-113.
RX PubMed=10360943; DOI=10.1021/bi990391y;
RA Bernat B.A., Laughlin L.T., Armstrong R.N.;
RT "Elucidation of a monovalent cation dependence and characterization of the
RT divalent cation binding site of the fosfomycin resistance protein (FosA).";
RL Biochemistry 38:7462-7469(1999).
CC -!- FUNCTION: Metalloglutathione transferase which confers resistance to
CC fosfomycin by catalyzing the addition of glutathione to fosfomycin.
CC {ECO:0000269|PubMed:9115979}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + RX = a halide anion + an S-substituted
CC glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:90779; EC=2.5.1.18;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:9115979};
CC -!- ACTIVITY REGULATION: Requires the monovalent cation K(+) for optimal
CC activity.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9115979}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1963292}.
CC -!- SIMILARITY: Belongs to the fosfomycin resistance protein family.
CC {ECO:0000305}.
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DR EMBL; M85195; AAA98399.1; -; Genomic_DNA.
DR RefSeq; WP_038415208.1; NG_050405.1.
DR PDB; 1NPB; X-ray; 2.50 A; A/B/C/D/E/F=1-141.
DR PDBsum; 1NPB; -.
DR AlphaFoldDB; Q56415; -.
DR SMR; Q56415; -.
DR SABIO-RK; Q56415; -.
DR EvolutionaryTrace; Q56415; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004364; F:glutathione transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR Gene3D; 3.10.180.10; -; 1.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR Pfam; PF00903; Glyoxalase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR PROSITE; PS51819; VOC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cytoplasm; Manganese; Metal-binding;
KW Potassium; Transferase.
FT CHAIN 1..141
FT /note="Glutathione transferase FosA"
FT /id="PRO_0000164044"
FT DOMAIN 4..117
FT /note="VOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 7
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 67
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 113
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT MUTAGEN 7
FT /note="H->A: Strong decrease in fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT MUTAGEN 7
FT /note="H->Q: Decrease in fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT MUTAGEN 67
FT /note="H->A: Loss of fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT MUTAGEN 67
FT /note="H->Q: Decrease in fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT MUTAGEN 113
FT /note="E->A: Strong decrease in fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT MUTAGEN 113
FT /note="E->Q: Decrease in fosfomycin resistance."
FT /evidence="ECO:0000269|PubMed:10360943"
FT STRAND 4..13
FT /evidence="ECO:0007829|PDB:1NPB"
FT HELIX 15..23
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:1NPB"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1NPB"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:1NPB"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:1NPB"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:1NPB"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1NPB"
SQ SEQUENCE 141 AA; 15959 MW; 7BA4E5BF33FF3315 CRC64;
MLQSLNHLTL AVSDLQKSVT FWHELLGLTL HARWNTGAYL TCGDLWVCLS YDEARQYVPP
QESDYTHYAF TVAEEDFEPL SQRLEQAGVT IWKQNKSEGA SFYFLDPDGH KLELHVGSLA
ARLAACREKP YAGMVFTSDE A
