Open AccessComputer modelling of human alpha 1-antitrypsin reactive site loop behaviour under mild conditions.
Author(s) -
Henryk Kołoczek,
Grzegorz Jezierski,
Marta Pasenkiewicz-Gierula
Publication year - 1996
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1996_4478
Subject(s) - serpin , chemistry , salt bridge , alpha (finance) , active site , loop (graph theory) , binding site , biochemistry , biophysics , mutant , stereochemistry , enzyme , biology , medicine , construct validity , nursing , mathematics , combinatorics , patient satisfaction , gene
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.