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

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dc.contributor.author Boyko K.
dc.contributor.author Baymukhametov T.
dc.contributor.author Chesnokov Y.
dc.contributor.author Hons M.
dc.contributor.author Lushchekina S.
dc.contributor.author Konarev P.
dc.contributor.author Lipkin A.
dc.contributor.author Vasiliev A.
dc.contributor.author Masson P.
dc.contributor.author Popov V.
dc.contributor.author Kovalchuk M.
dc.date.accessioned 2020-01-15T21:17:47Z
dc.date.available 2020-01-15T21:17:47Z
dc.date.issued 2019
dc.identifier.issn 0300-9084
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/155591
dc.description.abstract © 2018 The Authors 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)4-peptide C-terminal tail is located in the center of the tetramer, nearly perpendicular to its plane, and is plunged deep between the four subunits. Molecular dynamics simulations allowed optimization of the geometry of the molecule and reconstruction of the structural features invisible in the cryoEM density, i.e., glycan chains and glycan interdimer contact areas, as well as intermonomer disulfide bridges at the C-terminal tail. Finally, SAXS data were used to confirm the consistency of the obtained model with the experimental data. The tetramer organization of BChE is unique in that the four subunits are joined at their C-termini through noncovalent contacts with a short polyproline-rich peptide. This tetramer structure could serve as a model for the design of highly stable glycosylated tetramers.
dc.relation.ispartofseries Biochimie
dc.subject 3D structure
dc.subject Acetylcholinesterase
dc.subject Butyrylcholinesterase
dc.subject cryoEM
dc.subject Molecular dynamics
dc.subject Tetramer
dc.title 3D structure of the natural tetrameric form of human butyrylcholinesterase as revealed by cryoEM, SAXS and MD
dc.type Article
dc.relation.ispartofseries-volume 156
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 196
dc.source.id SCOPUS03009084-2019-156-SID85055907474

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  • Публикации сотрудников КФУ Scopus [22633]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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