Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00556414" target="_blank" >RIV/86652036:_____/21:00556414 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/21:00556414
Result on the web
<a href="https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1942213" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1942213</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/07391102.2021.1942213" target="_blank" >10.1080/07391102.2021.1942213</a>
Alternative languages
Result language
angličtina
Original language name
Molecular dynamics simulations provide structural insight into binding of cyclic dinucleotides to human STING protein
Original language description
Human stimulator of interferon genes (hSTING) is a signaling adaptor protein that triggers innate immune system by response to cytosolic DNA and second messenger cyclic dinucleotides (CDNs). Natural CDNs contain purine nucleobase with different phosphodiester linkage types (3 '-3 ', 2 '-2 ' or mixed 2 '-3 '-linkages) and exhibit different binding affinity towards hSTING, ranging from micromolar to nanomolar. High-affinity CDNs are considered as suitable candidates for treatment of chronic hepatitis B and cancer. We have used molecular dynamics simulations to investigate dynamical aspects of binding of natural CDNs (specifically, 2'-2'-cGAMP, 2'-3'-cGAMP, 3'-3'-cGAMP, 3'-3'-c-di-AMP, and 3'-3'-c-di-GMP) with hSTING(wt) protein. Our results revealed that CDN/hSTING(wt) interactions are controlled by the balance between fluctuations (conformational changes) in the CDN ligand and the protein dynamics. Binding of different CDNs induces different degrees of conformational/dynamics changes in hSTING(wt) ligand binding cavity, especially in alpha(1)-helices, the so-called lid region and alpha(2)-tails. The ligand residence time in hSTING(wt) protein pocket depends on different contribution of R232 and R238 residues interacting with oxygen atoms of phosphodiester groups in ligand, water distribution around interacting charged centers (in protein residues and ligand) and structural stability of closed conformation state of hSTING(wt) protein. These findings may perhaps guide design of new compounds modulating hSTING activity. Communicated by Ramaswamy H. Sarma
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Biomolecular Structure & Dynamics
ISSN
0739-1102
e-ISSN
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Volume of the periodical
JUN 2021
Issue of the periodical within the volume
JUN 2021
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
2021-07-12
UT code for WoS article
000668459800001
EID of the result in the Scopus database
2-s2.0-85109015815