Holon Physics Seminar, Faculty of Sciences
A Single Ion Inside a Protein: The Activation of Human Thrombin by Na+ Ion
Thursday, December 11, 2014 | 13:00 | Room 424/8
Thrombin is a member of serine proteases protein family and it fulfills a crucial role in blood coagulation process. The catalytic activity of human thrombin is higher 20-fold in the presence of sodium. The ion binding site, as proposed by Zhang and Tollinski (1997), is near the carbonyl oxygen atoms of R221a and K224. This location is ~17 A apart from the active site with consequential definition of an "allosteric activation”.
All-atom Molecular Dynamics simulations of the thrombin enzyme, loaded with Na+ ion, reveal high mobility of sodium. It has two preferred locations in the protein; one site is in the vicinity of R221a and K224, as described previously. The other site is near the carboxylate moiety of D189, very close to the substrate binding groove and the active site of the enzyme.
The passage of the ion between these two sites is mediated by rotameric transitions of D189. The ion can freely move between the sites through well solvated "tunnel”, which is open to the bulk on both sides. In the presence of a bound product, the Na+ ion is inserted between the Guanidino moiety of the product and the carboxylate of D189, apparently leading to ejection of the product from the protein.
We suggest that the enhanced catalysis by the sodium ion is attributed not to its crystal structure location, but to the ability of the ion to sample multiple locations in the protein.