Pseudomonas aeruginosa PAO1, PA1129 (fosA)

Cytoplasmic
Cytoplasmic Membrane
Periplasmic
Outer Membrane
Extracellular
Unknown
View in JBrowse PseudoCyc / Metabolic Pathways

Gene Feature Overview

Strain Pseudomonas aeruginosa PAO1 (Stover et al., 2000)
GCF_000006765.1|latest
Locus Tag
PA1129
Name
fosA
Replicon chromosome
Genomic location 1221691 - 1222098 (+ strand)
Transposon Mutants 2 transposon mutants in PAO1
Transposon Mutants in orthologs 1 transposon mutants in orthologs

Cross-References

RefSeq NP_249820.1
GI 15596326
Affymetrix PA1129_at
DNASU PaCD00006519
Entrez 877785
GenBank AAG04518.1
INSDC AAG04518.1
NCBI Locus Tag PA1129
protein_id(GenBank) gb|AAG04518.1|AE004543_2|gnl|PseudoCAP|PA1129
TIGR NTL03PA01130
UniParc UPI00000C5263
UniProtKB Acc Q9I4K6
UniProtKB ID FOSA_PSEAE
UniRef100 UniRef100_Q9I4K6
UniRef50 UniRef50_Q9I4K6
UniRef90 UniRef90_Q9I4K6

Product

Feature Type CDS
Coding Frame 1
Product Name
fosfomycin resistance protein, FosA
Product Name Confidence: Class 1
Synonyms probable fosfomycin resistance protein
Evidence for Translation
Charge (pH 7) -0.87
Kyte-Doolittle Hydrophobicity Value -0.219
Molecular Weight (kDa) 15.1
Isoelectric Point (pI) 6.67

Subcellular localization

Individual Mappings
Localization Confidence PMID
Cytoplasmic Class 3
Additional evidence for subcellular localization

AMR gene predictions from CARD database

Identified using the Resistance Gene Identifier (RGI)

Model Name Definition Accession Model Type (?) SNP Cutoff Bit Score Percent Identity CARD Version
FosA An enzyme that confers resistance to fosfomycin in Serratia marcescens by breaking the epoxide ring of the molecule. It depends on the cofactors Manganese (II) and Potassium and uses Glutathione (GSH) as the nucleophilic molecule. In Pseudomonas aeruginosa, FosA catalyzes the conjugation of glutathione to carbon-1 of fosfomycin, rendering it ineffective as an antibacterial drug. [PMID:15075406, PMID:15741169] ARO:3000149 protein homolog model Perfect 283.1 100.0 3.2.5

AlphaFold 2 Protein Structure Predictions

Protein structure predictions using a neural network model developed by DeepMind. If a UniProtKB accession is associated with this protein, a search link will be provided below.

Look for predicted 3D structure in AlphaFold DB: Search

PDB 3D Structures

Accession Header Accession Date Compound Source Resolution Method Percent Identity
1LQO TRANSFERASE 05/11/02 Crystal Strutcure of the Fosfomycin Resistance Protein A (FosA) Containing Bound Thallium Cations Pseudomonas aeruginosa 2 X-RAY DIFFRACTION 100.0
1NKI TRANSFERASE 01/03/03 CRYSTAL STRUCTURE OF THE FOSFOMYCIN RESISTANCE PROTEIN A (FOSA) CONTAINING BOUND PHOSPHONOFORMATE Pseudomonas aeruginosa 0.95 X-RAY DIFFRACTION 100.0
1LQK TRANSFERASE 05/10/02 High Resolution Structure of Fosfomycin Resistance Protein A (FosA) Pseudomonas aeruginosa 1.35 X-RAY DIFFRACTION 100.0
1LQP TRANSFERASE 05/11/02 CRYSTAL STRUCTURE OF THE FOSFOMYCIN RESISTANCE PROTEIN (FOSA) CONTAINING BOUND SUBSTRATE Pseudomonas aeruginosa 1.19 X-RAY DIFFRACTION 100.0
1NNR TRANSFERASE 01/14/03 Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site Pseudomonas aeruginosa 2.25 X-RAY DIFFRACTION 100.0

Pathogen Association Analysis

Results
Common
Found in both pathogen and nonpathogenic strains
Hits to this gene were found in 84 genera

Orthologs/Comparative Genomics

Pseudomonas Ortholog Database View orthologs at Pseudomonas Ortholog Database
Pseudomonas Ortholog Group POG001089 (344 members)
Putative Inparalogs None Found

Interactions

STRING database Search for predicted protein-protein interactions using:
Search term: PA1129
Search term: fosA

Human Homologs

References

Nucleotide sequence and intracellular location of the product of the fosfomycin resistance gene from transposon Tn2921.
Navas J, León J, Arroyo M, García Lobo JM
Antimicrob Agents Chemother 1990 Oct;34(10):2016-8
PubMed ID: 1963292
Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).
Rife CL, Pharris RE, Newcomer ME, Armstrong RN
J Am Chem Soc 2002 Sep 18;124(37):11001-3
PubMed ID: 12224946
Structure of fosfomycin resistance protein FosA from transposon Tn2921.
Pakhomova S, Rife CL, Armstrong RN, Newcomer ME
Protein Sci 2004 May;13(5):1260-5
PubMed ID: 15075406
Pseudomonas aeruginosa fosfomycin resistance mechanisms affect non-inherited fluoroquinolone tolerance.
De Groote VN, Fauvart M, Kint CI, Verstraeten N, Jans A, Cornelis P, Michiels J
J Med Microbiol 2011 Mar;60(Pt 3):329-336
PubMed ID: 21212150
Phosphonoformate: a minimal transition state analogue inhibitor of the fosfomycin resistance protein, FosA.
Rigsby RE, Rife CL, Fillgrove KL, Newcomer ME, Armstrong RN
Biochemistry 2004 Nov 2;43(43):13666-73
PubMed ID: 15504029
Fosfomycin resistance proteins: a nexus of glutathione transferases and epoxide hydrolases in a metalloenzyme superfamily.
Rigsby RE, Fillgrove KL, Beihoffer LA, Armstrong RN
Methods Enzymol 2005;401:367-79
PubMed ID: 16399398
A model for glutathione binding and activation in the fosfomycin resistance protein, FosA.
Rigsby RE, Brown DW, Dawson E, Lybrand TP, Armstrong RN
Arch Biochem Biophys 2007 Aug 15;464(2):277-83
PubMed ID: 17537395
Functional analysis of active site residues of the fosfomycin resistance enzyme FosA from Pseudomonas aeruginosa.
Beharry Z, Palzkill T
J Biol Chem 2005 May 6;280(18):17786-91
PubMed ID: 15741169