Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00429661" target="_blank" >RIV/61388963:_____/14:00429661 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22340/14:43897069

Result on the web

<a href="http://dx.doi.org/10.1021/bi500073z" target="_blank" >http://dx.doi.org/10.1021/bi500073z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/bi500073z" target="_blank" >10.1021/bi500073z</a>

Result language

angličtina

Original language name

Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

Original language description

The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin-insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral phi and psi main-chain angles. alpha-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization ofthe R-state, and N-methylalanine and D-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed agains

Czech name

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Czech description

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Type

J_x - 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

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biochemistry

ISSN

0006-2960

e-ISSN

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Volume of the periodical

53

Issue of the periodical within the volume

21

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

3392-3402

UT code for WoS article

000336643800002

EID of the result in the Scopus database

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