Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging

Biochemistry
Florian NachonO Lockridge

Abstract

Organophosphorus poisons (OP) bind covalently to the active-site serine of cholinesterases. The inhibited enzyme can usually be reactivated with powerful nucleophiles such as oximes. However, the covalently bound OP can undergo a suicide reaction (termed aging) yielding nonreactivatable enzyme. In human butyrylcholinesterase (hBChE), aging involves the residues His438 and Glu197 that are proximal to the active-site serine (Ser198). The mechanism of aging is known in detail for the nerve gases soman, sarin, and tabun as well as the pesticide metabolite isomalathion. Aging of soman- and sarin-inhibited acetylcholinesterase occurs by C-O bond cleavage, whereas that of tabun- and isomalathion-inhibited acetylcholinesterase occurs by P-N and P-S bond cleavage, respectively. In this work, the crystal structures of hBChE inhibited by the ophthalmic reagents echothiophate (nonaged and aged) and diisopropylfluorophosphate (aged) were solved and refined to 2.1, 2.25, and 2.2 A resolution, respectively. No appreciable shift in the position of the catalytic triad histidine was observed between the aged and nonaged conjugates of hBChE. This absence of shift contrasts with the aged and nonaged crystal structures of Torpedo californica acetyl...Continue Reading

References

Jul 1, 1967·Archives of Biochemistry and Biophysics·H O MichelM Pankau
Nov 14, 1997·The Biochemical Journal·P MassonO Lockridge
Jul 19, 2003·The Journal of Biological Chemistry·Yvain NicoletFlorian Nachon
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson

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Citations

Nov 2, 2012·Journal of the American Chemical Society·Evgeny V BeletskiySteven R Kass
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Colin J JacksonJohn G Oakeshott
Apr 17, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bin LiOksana Lockridge
Apr 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Daniel K NomuraJohn E Casida
Feb 5, 2016·Rapid Communications in Mass Spectrometry : RCM·Xiangkun Yang, Michael G Bartlett
Oct 1, 2008·Protein Science : a Publication of the Protein Society·Ozlem Doğan EkiciRoss E Dalbey
Dec 17, 2009·Archives of Biochemistry and Biophysics·Patrick Masson, Oksana Lockridge
Mar 27, 2010·Chemico-biological Interactions·Patrick MassonOksana Lockridge
Jun 18, 2016·Toxicology·Iris MangasTanos Celmar Costa França
Aug 19, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·He LiOksana Lockridge
Jan 4, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yves Bourne, Pascale Marchot
May 23, 2018·Physical Chemistry Chemical Physics : PCCP·Xiao WanJunjun Liu
Nov 18, 2018·Chemistry : a European Journal·Andrew J FranjesevicChristopher M Hadad
May 11, 2019·The Journal of Biological Chemistry·Ye WanQingjun Ma
Jun 27, 2020·International Journal of Molecular Sciences·Sylwester ŚlusarczykAdam Matkowski
Mar 30, 2018·Frontiers in Pharmacology·Sofya V LushchekinaPatrick Masson
Apr 21, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Oluwatoyin Ajibola AsojoOksana Lockridge
Feb 12, 2021·Bioorganic Chemistry·Pritam ThapaMukut Sharma
Jun 22, 2006·Pharmacogenetics and Genomics·Indumathi ManoharanRathnam Boopathy
Nov 4, 2008·Journal of the American Chemical Society·Eugénie CarlettiFlorian Nachon
Aug 19, 2008·Chemical Research in Toxicology·Shi-Jian DingOksana Lockridge

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