Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9QKX9)

• DOT Name: Lactoperoxidase (LPO)
• Synonyms: LPO; EC 1.11.1.7; Salivary peroxidase; SPO
• Gene Name: LPO
• UniProt ID: PERL_HUMAN
• EC Number: 1.11.1.7
• Pfam ID: PF03098
• Sequence:
  MRVLLHLPALLASLILLQAAASTTRAQTTRTSAISDTVSQAKVQVNKAFLDSRTRLKTAM
  SSETPTSRQLSEYLKHAKGRTRTAIRNGQVWEESLKRLRQKASLTNVTDPSLDLTSLSLE
  VGCGAPAPVVRCDPCSPYRTITGDCNNRRKPALGAANRALARWLPAEYEDGLSLPFGWTP
  GKTRNGFPLPLAREVSNKIVGYLNEEGVLDQNRSLLFMQWGQIVDHDLDFAPDTELGSSE
  YSKAQCDEYCIQGDNCFPIMFPPNDPKAGTQGKCMPFFRAGFVCPTPPYKSLAREQINAL
  TSFLDASFVYSSEPSLASRLRNLSSPLGLMAVNQEVSDHGLPYLPYDSKKPSPCEFINTT
  ARVPCFLAGDSRASEHILLATSHTLFLREHNRLARELKRLNPQWDGEKLYQEARKILGAF
  VQIITFRDYLPILLGDHMQKWIPPYQGYSESVDPRISNVFTFAFRFGHLEVPSSMFRLDE
  NYQPWGPEPELPLHTLFFNTWRMVKDGGIDPLVRGLLAKKSKLMKQNKMMTGELRNKLFQ
  PTHRIHGFDLAAINTQRCRDHGQPGYNSWRAFCDLSQPQTLEELNTVLKSKMLAKKLLGL
  YGTPDNIDIWIGAIAEPLVERGRVGPLLACLLGKQFQQIRDGDRFWWENPGVFTNEQKDS
  LQKMSFSRLVCDNTRITKVPRDPFWANSYPYDFVDCSAIDKLDLSPWASVKN
• Function: Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2). Also involved in the conversion of iodide (I(-)) into hypoiodite (IO(-)) in the presence of H2O2. Responsible for the inactivation of a wide range of micro-organisms and hence, important component of defense mechanism. Shows antibacterial properties against Pseudomonas aeruginosa. The lactoperoxidase-SCN(-)-H2O2 system shows antibacterial properties against Burkholderia cepacia and Haemophilus influenzae in vitro. Present in mammary and salivary gland secretions and may contribute to airway host defense against infection. May contribute to maintaining an appropriate H2O2 cellular level, therefore protecting cells from H2O2-caused injuries and inflammation.
• Tissue Specificity: Mammary gland, milk and salivary gland. Found in bronchial submucosal glands.
• KEGG Pathway:
  Salivary secretion (hsa04970)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway: Events associated with phagocytolytic activity of PMN cells (R-HSA-8941413)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Lactoperoxidase (LPO).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lactoperoxidase (LPO).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Lactoperoxidase (LPO).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Lactoperoxidase (LPO).	[6]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lactoperoxidase (LPO).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lactoperoxidase (LPO).	[3]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Lactoperoxidase (LPO).	[3]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Lactoperoxidase (LPO).	[3]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Lactoperoxidase (LPO).	[3]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Lactoperoxidase (LPO).	[3]
Gabapentin	DM6T924	Approved	Gabapentin decreases the expression of Lactoperoxidase (LPO).	[3]
Sulfadiazine	DMTW3R8	Approved	Sulfadiazine decreases the expression of Lactoperoxidase (LPO).	[3]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Lactoperoxidase (LPO).	[3]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Lactoperoxidase (LPO).	[7]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Lactoperoxidase (LPO).	[3]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [7] Cytoprotective effect of bioactive sea buckthorn extract on paraquat-exposed A549 cells via induction of Nrf2 and its downstream genes. Mol Med Rep. 2013 Dec;8(6):1852-60.