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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/60461373:22340/14:43897069

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Biochemistry

ISSN

0006-2960

e-ISSN

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Svazek periodika

53

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

3392-3402

Kód UT WoS článku

000336643800002

EID výsledku v databázi Scopus

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