title: Computer modelling of human alpha 1-antitrypsin reactive site loop behaviour under mild conditions.
abstract: 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.
authors.affiliation: Department of Physical Biochemistry, Jagiellonian University, Cracow, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Kołoczek
authors.forename: G
authors.initials: G
authors.lastname: Jezierski
authors.forename: M
authors.initials: M
authors.lastname: Pasenkiewicz-Gierula
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D011487:Protein Conformation; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
chemical_list: D000515:alpha 1-Antitrypsin