ID   FOSA_PSEAE              Reviewed;         135 AA.
AC   Q9I4K6;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 123.
DE   RecName: Full=Glutathione transferase FosA;
DE            EC=2.5.1.18;
DE   AltName: Full=Fosfomycin resistance protein;
GN   Name=fosA; OrderedLocusNames=PA1129;
OS   Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS   14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Pseudomonadales;
OC   Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=208964;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 /
RC   1C / PRS 101 / PAO1;
RX   PubMed=10984043; DOI=10.1038/35023079;
RA   Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA   Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA   Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA   Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA   Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA   Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT   "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT   pathogen.";
RL   Nature 406:959-964(2000).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.19 ANGSTROMS) IN COMPLEX WITH FOSFOMYCIN,
RP   FUNCTION, AND COFACTOR.
RC   STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 /
RC   1C / PRS 101 / PAO1;
RX   PubMed=12224946; DOI=10.1021/ja026879v;
RA   Rife C.L., Pharris R.E., Newcomer M.E., Armstrong R.N.;
RT   "Crystal structure of a genomically encoded fosfomycin resistance protein
RT   (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).";
RL   J. Am. Chem. Soc. 124:11001-11003(2002).
CC   -!- FUNCTION: Metalloglutathione transferase which confers resistance to
CC       fosfomycin by catalyzing the addition of glutathione to fosfomycin.
CC       {ECO:0000269|PubMed:12224946}.
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:12224946};
CC   -!- ACTIVITY REGULATION: Requires the monovalent cation K(+) for optimal
CC       activity.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the fosfomycin resistance protein family.
CC       {ECO:0000305}.
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DR   EMBL; AE004091; AAG04518.1; -; Genomic_DNA.
DR   PIR; E83503; E83503.
DR   RefSeq; NP_249820.1; NC_002516.2.
DR   RefSeq; WP_003082280.1; NZ_QZGE01000006.1.
DR   PDB; 1LQK; X-ray; 1.35 A; A/B=1-135.
DR   PDB; 1LQO; X-ray; 2.00 A; A/B=1-135.
DR   PDB; 1LQP; X-ray; 1.19 A; A/B=1-135.
DR   PDB; 1NKI; X-ray; 0.95 A; A/B=1-135.
DR   PDB; 1NNR; X-ray; 2.25 A; A/B=1-135.
DR   PDBsum; 1LQK; -.
DR   PDBsum; 1LQO; -.
DR   PDBsum; 1LQP; -.
DR   PDBsum; 1NKI; -.
DR   PDBsum; 1NNR; -.
DR   AlphaFoldDB; Q9I4K6; -.
DR   SMR; Q9I4K6; -.
DR   STRING; 208964.PA1129; -.
DR   PaxDb; 208964-PA1129; -.
DR   DNASU; 877785; -.
DR   GeneID; 877785; -.
DR   KEGG; ag:AAG04518; -.
DR   KEGG; pae:PA1129; -.
DR   PATRIC; fig|208964.12.peg.1174; -.
DR   PseudoCAP; PA1129; -.
DR   HOGENOM; CLU_121356_0_0_6; -.
DR   InParanoid; Q9I4K6; -.
DR   OrthoDB; 4265398at2; -.
DR   PhylomeDB; Q9I4K6; -.
DR   BioCyc; PAER208964:G1FZ6-1155-MONOMER; -.
DR   EvolutionaryTrace; Q9I4K6; -.
DR   PRO; PR:Q9I4K6; -.
DR   Proteomes; UP000002438; Chromosome.
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   CDD; cd07244; FosA; 1.
DR   Gene3D; 3.10.180.10; 2,3-Dihydroxybiphenyl 1,2-Dioxygenase, domain 1; 1.
DR   InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR   InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR   InterPro; IPR037523; VOC.
DR   PANTHER; PTHR21366:SF22; GLYOXALASE DOMAIN-CONTAINING PROTEIN 5; 1.
DR   PANTHER; PTHR21366; GLYOXALASE FAMILY PROTEIN; 1.
DR   Pfam; PF00903; Glyoxalase; 1.
DR   SUPFAM; SSF54593; Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase; 1.
DR   PROSITE; PS51819; VOC; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antibiotic resistance; Cytoplasm; Manganese; Metal-binding;
KW   Potassium; Reference proteome; Transferase; Zinc.
FT   CHAIN           1..135
FT                   /note="Glutathione transferase FosA"
FT                   /id="PRO_0000164043"
FT   DOMAIN          4..114
FT                   /note="VOC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT   ACT_SITE        110
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT   BINDING         7
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163,
FT                   ECO:0000269|PubMed:12224946, ECO:0007744|PDB:1LQK,
FT                   ECO:0007744|PDB:1LQP, ECO:0007744|PDB:1NKI,
FT                   ECO:0007744|PDB:1NNR"
FT   BINDING         41
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT   BINDING         64
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163,
FT                   ECO:0000269|PubMed:12224946, ECO:0007744|PDB:1LQK,
FT                   ECO:0007744|PDB:1LQP, ECO:0007744|PDB:1NKI,
FT                   ECO:0007744|PDB:1NNR"
FT   BINDING         110
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163,
FT                   ECO:0000269|PubMed:12224946, ECO:0007744|PDB:1LQK,
FT                   ECO:0007744|PDB:1LQP, ECO:0007744|PDB:1NKI,
FT                   ECO:0007744|PDB:1NNR"
FT   STRAND          2..13
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   HELIX           15..24
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          29..34
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          37..42
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          45..51
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          60..62
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          64..69
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   HELIX           71..73
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   HELIX           74..83
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          88..90
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          94..96
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          98..102
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   STRAND          108..113
FT                   /evidence="ECO:0007829|PDB:1NKI"
FT   HELIX           116..125
FT                   /evidence="ECO:0007829|PDB:1NKI"
SQ   SEQUENCE   135 AA;  15124 MW;  0D75F174291A2366 CRC64;
     MLTGLNHLTL AVADLPASIA FYRDLLGFRL EARWDQGAYL ELGSLWLCLS REPQYGGPAA
     DYTHYAFGIA AADFARFAAQ LRAHGVREWK QNRSEGDSFY FLDPDGHRLE AHVGDLRSRL
     AACRQAPYAG MRFAD
//