Table 1.
Liver protein targets of 4-bromophenol metabolites.
| 4BP Target protein | # of spotsa | Matchesb | Coverage (%)c | Fractiond | Also targeted bye |
|---|---|---|---|---|---|
| Protein maturation or stabilization | |||||
| 56 kDa selenium-binding protein, Selenium-binding protein 1, SP56 | 2 | 6–9 | 13–21 | cytosol | AMAP, APAP, BB, BHT, MYCO, NAPH |
| Cellular thyroid hormone binding protein, PDI, PDI A1, Prolyl 4-hydroxylase beta subunit, Protein disulfide-isomerase [Precursor] | 4 | 8–18 | 14–34 | microsomes, mitochondria | 1,4-BQ, 1,4-NQ, AMAP, APAP, BB, BENZ, HALO, NAPH, MCTP, TB |
| 58 kDa microsomal protein, Disulfide isomerase ER-60, ERp57, ERp60, p58, PDI A3, Protein disulfide isomerase A3 [Precursor] | 6 | 3–15 | 5–32 | microsomes, mitochondria | 1,4-BQ, 1,4-NQ, APAP, ATRZ, BB, DACT, MCTP, MYCO, NAPH, TB |
| 78 kDa glucose-regulated protein [precursor], BiP, GRP 78, Heat shock 70 kDa protein 5, Immunoglobulin heavy chain binding protein, Steroidogenesis-activator polypeptide | 1 | 6 | 12 | microsomes | BB, HALO, NAPH, TB, TEUC |
| 60 kDa chaperonin, 60 kDa heat shock protein (mitochondrial [precursor]), CPN60, Heat shock protein 60, HSP-60, HSP-65, Hsp60, Mitochondrial matrix protein P1 | 1 | 6 | 18 | mitochondria | BQ, COC, DACT, NAPH, 1,4-NQ, TASO, TEUC, TFEC |
| 75 kDa glucose regulated protein, GRP 75, Heat shock 70 kDa protein 9, Mortalin, MTHSP70, PBP74, Peptide-binding protein 74, Stress-70 protein (mitochondrial [precursor]) | 1 | 4 | 9 | mitochondria | 1,4-BQ, 1,4-NQ, DACT, NAPH, TFEC |
| Enzymes of intermediary metabolism | |||||
| Beta-diketonase, FAA, Fumarylacetoacetase, Fumarylacetoacetate hydrolase | 1 | 5 | 13 | cytosol | BB, TB |
| Cytoplasmic malate dehydrogenase, Malate dehydrogenase (cytoplasmic) | 1 | 3 | 9 | cytosol | TB |
| hypoxanthine-guanine phosphoribosyltransferase, HGPRT | 1 | 5 | 25 | cytosol | (none) |
| TIM, Triose-phosphate isomerase, Triosephosphate isomerase, triosephosphate isomerase 1 | 2 | 2–6 | 12–29 | cytosol | BB, BHT, DACT, MYCO |
| Electrophile or peroxide defense | |||||
| Contraception-associated protein 1, Fertility protein SP22, Protein CAP1, Protein DJ-1 | 1 | 6 | 27 | cytosol | BB |
| Glutathione S-transferase Mu 2, Glutathione S-transferase Yb-2, GST 4-4, GST Yb2, GSTM2-2 | 4 | 3–9 | 13–42 | cytosol | BB, TB |
| Catalase | 2 | 5–8 | 10–18 | mitochondria | TB, TEUC |
| Binding proteins | |||||
| Albumin | 2 | 6 | 12 | mitochondria | ATRZ, BB, DCE, FCXC, NAPH, TB |
Many proteins appear in more than one spot on a 2D gel (see text). Each of the proteins listed in this table were observed in at least one spot which contained no other detectable proteins, even though some of them were also observed in other spots containing one or more other proteins.
Number of peptides sequenced and matched to the identified protein.
Percent of entire protein sequence covered by observed peptides.
Subcellular fraction in which the target protein was observed.
Other chemicals whose reactive metabolites are also known to target the same protein. Abbreviations: 1,4-BQ, 1,4-benzoquinone; 1,4-NQ, 1,4-naphthoquinone; AMAP, m-hydroxyacetanilide; APAP, p-hydroxyacetanilide; ATRZ, atrazine; BB, bromobenzene; BENZ, benzene; BHT, butylated hydroxytoluene; COC, cocaine; DACT, diaminochlorotriazine; DCE, 1,1-dichloroehtylene; FCXC, flucloxacillin; HAL, halothane; MCTP, monocrotaline pyrrole; MYCO, mycophenolic acid; NAPH, naphthalene; TB, thiobenzamide; TEUC, teucrin; TFEC, S-(1,1,2,2-tetrafluoroethyl) cysteine. Data from the Reactive Metabolite Target Protein Database (http://tpdb.medchem.ku.edu:8080/protein_database/).