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Exploring the Active Sites of Cholinesterases by Inhibition with Bambuterol and Haloxon

Zrinka Kovarik orcid.org/0000-0001-9863-886X ; Institute for Medical Research and Occupational Health, Ksaverska c. 2, POB 291, HR-10001 Zagreb, Croatia
Anita Bosak orcid.org/0000-0003-0164-4994 ; Institute for Medical Research and Occupational Health, Ksaverska c. 2, POB 291, HR-10001 Zagreb, Croatia
Goran Šinko orcid.org/0000-0002-8265-1901 ; Institute for Medical Research and Occupational Health, Ksaverska c. 2, POB 291, HR-10001 Zagreb, Croatia
Tatjana Latas ; Institute for Medical Research and Occupational Health, Ksaverska c. 2, POB 291, HR-10001 Zagreb, Croatia

Sažetak

The paper describes the inhibition of mouse acetylcholinesterase (AChE; EC 3.1.1.7) and mouse, human, and horse butyrylcholinesterase (BChE; EC 3.1.1.8) by 5-[2-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride (bambuterol) and by O,O-bis-(2-chloroethyl)-O-(3-chloro-4-methylcoumarin-7-yl) phosphate (haloxon). The haloxon inhibition rate constant (ki) for mouse BChE was 3.7 × 107 min–1 mol–1 dm3, which was 40-fold higher than the rate constant for mouse AChE. Bambuterol inhibition of horse BChE (ki = 2.1 × 105 min–1 mol–1 dm3) was about 25-fold slower than that of human or mouse BChE, whereas the respective haloxon inhibition of horse BChE (ki = 1.2 × 107 min–1 mol–1 dm3) was about 2-3-fold slower. Sequence alignments and the computational model of the three-dimensional structure of horse BChE suggest that residues inside the active site at positions 69, 277 and 285 are important for the differences in the inhibition of these three BChE species.

Ključne riječi

mouse acetylcholinesterase; mouse, human and horse butyrylcholinesterase; inhibition; carbamate; organophosphate; haloxon; bambuterol

Hrčak ID:

103058

URI

https://hrcak.srce.hr/103058

Datum izdavanja:

30.4.2003.

Posjeta: 2.045 *