A computational study of the open and closed forms of the N-lobe human serum transferrin apoprotein.

ABSTRACT: Human serum transferrin tightly binds ferric ions in the blood stream but is able to release them in cells by a process involving receptor-mediated endocytosis and decrease in pH. Iron binding and release are accompanied by a large conformation change. In this study, we investigate theoretically the open and closed forms of the N-lobe human serum transferrin apoprotein by performing pKa calculations and molecular dynamics and free-energy simulations. In agreement with the hypothesis based on the x-ray crystal structures, our calculations show that there is a shift in the pKa values of the lysines forming the dilysine trigger when the conformation changes. We argue, however, that simple electrostatic repulsion between the lysines is not sufficient to trigger domain opening and, instead, pro

SUBMITTER: Rinaldo D 

PROVIDER: S-EPMC1303656 | biostudies-literature | 2003 Dec

REPOSITORIES: biostudies-literature