Can Arginine Inhibit Insulin Aggregation? A Combined Protein Crystallography, Capillary Electrophoresis, and Molecular Simulation Study

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00498603" target="_blank" >RIV/61388963:_____/18:00498603 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/18:10383285
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.8b06557" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.8b06557</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.8b06557" target="_blank" >10.1021/acs.jpcb.8b06557</a>

Result language
angličtina
Original language name
Can Arginine Inhibit Insulin Aggregation? A Combined Protein Crystallography, Capillary Electrophoresis, and Molecular Simulation Study
Original language description
The oligomeric state of the storage form of human insulin in the pancreas, which may be affected by several endogenous components of beta-cell storage granules such as arginine, is not known. Here, the effect of arginine on insulin oligomerization is investigated independently by protein crystallography, molecular dynamics simulations, and capillary electrophoresis. The combined results point to a strong effect of ionic strength on insulin assembly. Molecular simulations and electrophoretic measurements at low/mM salt concentrations show no significant effect of arginine on insulin aggregation. In contrast, crystallographic data at high/molar ionic strength indicate inhibition of insulin hexamerization by arginine due to its binding at the site relevant for intermolecular contacts, which was also observed in MD simulations. Our results thus bracket the in vivo situation in pancreatic, beta-cell storage granules, where the ionic strength is estimated to be in the hundreds of millimolar to submolar range. The present findings add to a molecular understanding of in vivo insulin oligomerization and storage, with additional implications for insulin stability in arginine-rich injections.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry

Project
<a href="/en/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemical biology for drugging undruggable targets</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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