Sergey A. Kozin

Dr. Sergey A. Kozin

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
orcid

Research Focus & Metrics

Academic Career Length

26Years (2001-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

View All Publications
1 January 2006 in Journal of Biological Chemistry
Verified
Journal Article
Open access
SZSéverine Zirah
Séverine Zirah
SKSergey A. Kozin
Sergey A. Kozin
AMAlexey K. Mazur
Alexey K. Mazur
ABAlain Blond
Alain Blond
MCMichel Cheminant
Michel Cheminant
SRSylvie Rebuffat
Sylvie Rebuffat
Amyloid deposits within the cerebral tissue constitute a characteristic lesion associated with Alzheimer disease. They mainly consist of the amyloid peptide Abeta and display an abnormal content in Zn(2+) ions, together with many truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can be considered the minimal zinc-binding domain and contains two aspartates subject to protein aging. The influence of zinc binding and protein aging related modifications on the conformation of this region of Abeta is of importance given the potentiality of this domain to constitute a therapeutic target, especially for immunization approaches. In this study, we determined from NMR data the solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH 6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro aging experiments on Abeta-(1-16) led to the formation of truncated and isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7), displayed a local conformational change in the His(6)-Ser(8) region but kept a zinc binding propensity via a coordination mode involving l-iso-Asp(7). These results are discussed here with regard to Abeta fibrillogenesis and the potentiality of the region 1-16 of Abeta to be used as a therapeutic target.

1 July 2001 in Biochemical and Biophysical Research Communications
Verified
Journal Article
Closed access
SKSergey A. Kozin
Sergey A. Kozin
SZSéverine Zirah
Séverine Zirah
SRSylvie Rebuffat
Sylvie Rebuffat
GHGaston Hui Bon Hoa
Gaston Hui Bon Hoa
PDPascale Debey
Pascale Debey

1 November 2010 in Biophysical Journal
Verified
Journal Article
Closed access
PTPhilipp O. Tsvetkov
Philipp O. Tsvetkov
AKAlexandra A. Kulikova
Alexandra A. Kulikova
AGAndrey V. Golovin
Andrey V. Golovin
YTYaroslav V. Tkachev
Yaroslav V. Tkachev
AAAlexander I. Archakov
Alexander I. Archakov
AMAlexander Makarov
Alexander Makarov

22 February 2016 in Scientific Reports
Verified
Journal Article
Open access
AIAndrey N. Istrate
Andrey N. Istrate
SKSergey A. Kozin
Sergey A. Kozin
SZSergey S. Zhokhov
Sergey S. Zhokhov
AMAlexey B. Mantsyzov
Alexey B. Mantsyzov
OKOlga I. Kechko
Olga I. Kechko
VPVladimir Polshakov
Vladimir Polshakov
Conformational changes of Aβ peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer’s disease (AD). Interactions of zinc ions with Aβ are mediated by the N-terminal Aβ1–16 domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Aβ plaque formation. We have determined structure and functional characteristics of the metal binding domains derived from several Aβ variants and found that their zinc-induced oligomerization is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14. The residue H6 and segment 11EVHH14, which are part of this site are crucial for formation of the two zinc-mediated interaction interfaces in Aβ. These structural determinants can be considered as promising targets for rational design of the AD-modifying drugs aimed at blocking pathological Aβ aggregation.

14 May 2013 in Neurotoxicity Research
Verified
Journal Article
Closed access
PDF file
SKSergey A. Kozin
Sergey A. Kozin
ICI. B. Cheglakov
I. B. Cheglakov
AOA. A. Ovsepyan
A. A. Ovsepyan
GTG. B. Telegin
G. B. Telegin
PTP. O. Tsvetkov
P. O. Tsvetkov
AMAlexander Makarov
Alexander Makarov

15 May 2017 in Frontiers in Genetics
Verified
Journal Article
Open access
EBEvgeny P. Barykin
Evgeny P. Barykin
VMVladimir Mitkevich
Vladimir Mitkevich
SKSergey A. Kozin
Sergey A. Kozin
AMAlexander A. Makarov
Alexander A. Makarov
Amyloid β Modification: A Key to the Sporadic Alzheimer's Disease?