3D structure of the natural tetrameric form of human butyrylcholinesterase as revealed by cryoEM, SAXS and MD.

K.M. Boyko, V.O. Popov, T.N. Baymukhametov, Y.M. Chesnokov, P.V. Konarev, A.V. Lipkin, A.L. Vasiliev, M.V. Kovalchuk, M. Hons, S.V. Lushchekina

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Human plasma butyrylcholinesterase (BChE) is an endogenous bioscavenger that hydrolyzes numerous medicamentous and poisonous esters and scavenges potent organophosphorus nerve agents. BChE is thus a marker for the diagnosis of OP poisoning. It is also considered a therapeutic target against Alzheimer's disease. Although the X-ray structure of a partially deglycosylated monomer of human BChE was solved 15 years ago, all attempts to determine the 3D structure of the natural full-length glycosylated tetrameric human BChE have been unsuccessful so far. Here, a combination of three complementary structural methods—single-particle cryo-electron microscopy, molecular dynamics and small-angle X-ray scattering—were implemented to elucidate the overall structural and spatial organization of the natural tetrameric human plasma BChE. A 7.6 Å cryoEM map clearly shows the major features of the enzyme: a dimer of dimers with a nonplanar monomer arrangement, in which the interconnecting super helix complex PRAD-(WAT) <sub>4<
Original languageEnglish
Pages (from-to)196-205
JournalBiochimie
Volume156
StatePublished - 2019
Externally publishedYes

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