New insights on molecular interactions of organophosphorus pesticides with esterases
Language English Country Ireland Media print-electronic
Document type Journal Article, Review
PubMed
27311923
DOI
10.1016/j.tox.2016.06.006
PII: S0300-483X(16)30095-6
Knihovny.cz E-resources
- Keywords
- Organophosphorus compounds, alpha/beta hydrolases, cholinesterases, in silico, mass spectrometry, pesticides,
- MeSH
- Cholinesterases chemistry metabolism MeSH
- Esterases chemistry metabolism MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- Organophosphorus Compounds chemistry metabolism MeSH
- Pesticides chemistry metabolism MeSH
- Protein Structure, Secondary MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Protein Binding physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Cholinesterases MeSH
- Esterases MeSH
- Organophosphorus Compounds MeSH
- Pesticides MeSH
Organophosphorus compounds (OPs) are a large and diverse class of chemicals mainly used as pesticides and chemical weapons. People may be exposed to OPs in several occasions, which can produce several distinct neurotoxic effects depending on the dose, frequency of exposure, type of OP, and the host factors that influence susceptibility and sensitivity. These neurotoxic effects are mainly due to the interaction with enzyme targets involved in toxicological or detoxication pathways. In this work, the toxicological relevance of known OPs targets is reviewed. The main enzyme targets of OPs have been identified among the serine hydrolase protein family, some of them decades ago (e.g. AChE, BuChE, NTE and carboxylesterases), others more recently (e.g. lysophospholipase, arylformidase and KIA1363) and others which are not molecularly identified yet (e.g. phenylvalerate esterases). Members of this family are characterized by displaying serine hydrolase activity, containing a conserved serine hydrolase motif and having an alpha-beta hydrolase fold. Improvement in Xray-crystallography and in silico methods have generated new data of the interactions between OPs and esterases and have established new methods to study new inhibitors and reactivators of cholinesterases. Mass spectrometry for AChE, BChE and APH have characterized the active site serine adducts with OPs being useful to detect biomarkers of OPs exposure and inhibitory and postinhibitory reactions of esterases and OPs. The purpose of this review is focus specifically on the interaction of OP with esterases, mainly with type B-esterases, which are able to hydrolyze carboxylesters but inhibited by OPs by covalent phosphorylation on the serine or tyrosine residue in the active sites. Other related esterases in some cases with no-irreversible effect are also discussed. The understanding of the multiple molecular interactions is the basis we are proposing for a multi-target approach for understanding the organophosphorus toxicity.
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