Computer modelling of human alpha 1-antitrypsin reactive site loop behaviour under mild conditions.
Human alpha 1-antitrypsin (alpha 1-PI) is a member of the serpin superfamily of proteins. The reactive site loop (RSL) of the serpin binds to the active site of its target proteinase. Deficiency of alpha 1-antitrypsin is associated with a spontaneous conformational transition in the molecule which leads to a polymer formation. Mild conditions (1 M guanidinium.HCl), temperature and point mutations within the RSL are the factors that induce polymerisation. Initiation of this process has been associated with the disruption of a salt bridge Glu342-->Lys290. In this paper the interaction of guanidinium ion with Glu342 and Lys290 as well as the effect of this interaction on the mobility of RSL is studied by molecular modelling.
Kołoczek
H
H
Department of Physical Biochemistry, Jagiellonian University, Cracow, Poland.
Jezierski
G
G
Pasenkiewicz-Gierula
M
M
D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D011487:Protein Conformation; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
D000515:alpha 1-Antitrypsin