Naslov
Docking study of interaction between ethopropazine enantiomers and cholinesterases

Autori
Šinko, Goran ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the HDBMB 2008, Congress of the Croatian Society of Biochemistry and Molecular Biology with international participation / Strelec, Ivica ; Glavaš-Obrovac, Ljubica - Osijek : Hrvatsko Društvo za Biotehnologiju, 2008, 47-47

ISBN
978-953-95551-2-0

Skup
HDBMB 2008, Congress of the Croatian Society of Biochemistry and Molecular Biology with international participation

Mjesto i datum
Osijek, Hrvatska, 17.09.2008. - 20.09.2008

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
ethopropazine enantiomers; cholinesterase stereoselectivity; molecular modeling; flexible docking

Sažetak
Ethopropazine is a racemic anticholinergic drug used in the treatment of Parkinson’ s disease. Mouse (Mus musculus) butyrylcholinesterase is stereoselective toward ethopropazine enantiomers with nanomolar affinity. BChE has about 2.5 times higher affinity for R-ethopropazine than for S-ethopropazine. Site-directed mutants of acetylcholinesterase (AChE), Trp286Ala and Tyr337Ala, have been used to investigate the structural and mechanistic bases of stereoselective enzyme interaction. These mutations enlarged enzyme active site gorge and increased affinity toward enantiomers by three orders of magnitude when compared with the wild type AChE, and were also stereoselective toward ethopropazine enantiomers. To clarify possible ways of interaction between enantiomers and amino acid residues lining the active site, it was applied the flexible docking protocol within Accelrys’ s Discovery Studio software. This protocol generates conformers of each enantiomer as well as conformers of the studied enzymes, and results with binding energy for the pairs of enantiomer conformers and enzyme conformations. Molecular modeling is used to analyze ligand-enzyme interactions, inter-residue distances, and residue-residue interactions within the enzyme active site. The binding energies between enzymes and docked enantiomers of ethopropazine (poses) were in correlation with matching kinetic constants.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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