- Tytuł:
- The effect of the Glu342Lys mutation in α1-antitrypsin on its structure, studied by molecular modelling methods.
- Autorzy:
-
Jezierski, Grzegorz
Pasenkiewicz-Gierula, Marta - Powiązania:
- https://bibliotekanauki.pl/articles/1044164.pdf
- Data publikacji:
- 2001
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
serpins
protein structure
energy minimisation
molecular dynamics simulation - Opis:
- The structure of native α1-antitrypsin, the most abundant protease inhibitor in human plasma, is characterised primarily by a reactive loop containing the centre of proteinase inhibition, and a β-sheet composed of five strands. Mobility of the reactive loop is confined as a result of electrostatic interactions between side chains of Glu342 and Lys290, both located at the junction of the reactive loop and the β structure. The most common mutation in the protein, resulting in its inactivation, is Glu342→Lys, named the Z mutation. The main goal of this work was to investigate the influence of the Z mutation on the structure of α1-antitrypsin. Commonly used molecular modelling methods have been applied in a comparative study of two protein models: the wild type and the Z mutant. The results indicate that the Z mutation introduces local instabilities in the region of the reactive loop. Moreover, even parts of the protein located far apart from the mutation region are affected. The Z mutation causes a relative change in the total energy of about 3%. Relatively small root mean square differences between the optimised structures of the wild type and the Z mutant, together with detailed analysis of 'conformational searching' process, lead to the hypothesis that the Z mutation principally induces a change in the dynamics of α1-antitrypsin.
- Źródło:
-
Acta Biochimica Polonica; 2001, 48, 1; 65-75
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł