New insights on molecular interactions of organophosphorus pesticides with esterases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F17%3A50005090" target="_blank" >RIV/62690094:18450/17:50005090 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.tox.2016.06.006" target="_blank" >http://dx.doi.org/10.1016/j.tox.2016.06.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2016.06.006" target="_blank" >10.1016/j.tox.2016.06.006</a>

Result language

angličtina

Original language name

New insights on molecular interactions of organophosphorus pesticides with esterases

Original language description

Organophosphorus compounds (OPs) are a large and diverse class of chem. mainly used as pesticides and chem. 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 Besterases, 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 ganophosphorus toxicity.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30107 - Medicinal chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicology

ISSN

0300-483X

e-ISSN

—

Volume of the periodical

376

Issue of the periodical within the volume

únor

Country of publishing house

IE - IRELAND

Number of pages

14

Pages from-to

30-43

UT code for WoS article

000393526700005

EID of the result in the Scopus database

2-s2.0-84978437153