Structural and Functional Study of the GlnB22-Insulin Mutant Responsible for Maturity-Onset Diabetes of the Young

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00437498" target="_blank" >RIV/61388963:_____/14:00437498 - isvavai.cz</a>
Result on the web
<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0112883" target="_blank" >http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0112883</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0112883" target="_blank" >10.1371/journal.pone.0112883</a>

Result language
angličtina
Original language name
Structural and Functional Study of the GlnB22-Insulin Mutant Responsible for Maturity-Onset Diabetes of the Young
Original language description
The insulin gene mutation c.137G>A (R46Q), which changes an arginine at the B22 position of the mature hormone to glutamine, causes the monogenic diabetes variant maturity-onset diabetes of the young (MODY). In MODY patients, this mutation is heterozygous, and both mutant and wild-type (WT) human insulin are produced simultaneously. However, the patients often depend on administration of exogenous insulin. In this study, we chemically synthesized the MODY mutant [GlnB22]-insulin and characterized its biological and structural properties. The chemical synthesis of this insulin analogue revealed that its folding ability is severely impaired. In vitro and in vivo tests showed that its binding affinity and biological activity are reduced (both approximately 20% that of human insulin). Comparison of the solution structure of [GlnB22]-insulin with the solution structure of native human insulin revealed that the most significant structural effect of the mutation is distortion of the B20-B23 b
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
—

Project
<a href="/en/project/LK11205" target="_blank" >LK11205: Biomolecular NMR spectroscopy for rational drug design</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2014
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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