Structural Integrity of the B24 Site in Human Insulin Is Important for Hormone Functionality

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F13%3A00392749" target="_blank" >RIV/61388963:_____/13:00392749 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1074/jbc.M112.448050" target="_blank" >http://dx.doi.org/10.1074/jbc.M112.448050</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1074/jbc.M112.448050" target="_blank" >10.1074/jbc.M112.448050</a>

Result language
angličtina
Original language name
Structural Integrity of the B24 Site in Human Insulin Is Important for Hormone Functionality
Original language description
Despite the recent first structural insight into the insulin-insulin receptor complex, the role of the C terminus of the B-chain of insulin in this assembly remains unresolved. Previous studies have suggested that this part of insulin must rearrange to reveal amino acids crucial for interaction with the receptor. The role of the invariant Phe(B24), one of the key residues of the hormone, in this process remains unclear. For example, the B24 site functionally tolerates substitutions to D-amino acids butnot to L-amino acids. Here, we prepared and characterized a series of B24-modified insulin analogues, also determining the structures of [D-HisB24]-insulin and [HisB24]-insulin. The inactive [HisB24]-insulin molecule is remarkably rigid due to a tight accommodation of the L-His side chain in the B24 binding pocket that results in the stronger tethering of B25-B28 residues to the protein core. In contrast, the highly active [D-HisB24]-insulin is more flexible, and the reverse chirality of
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
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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