Toward understanding allosteric activation of thrombin: A conjecture for important roles of unbound Na+ molecules around thrombin

Ikuo Kurisaki, Masayoshi Takayanagi, Masataka Nagaoka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

We shed light on important roles of unbound Na+ molecules in enzymatic activation of thrombin. Molecular mechanism of Na+-activation of thrombin has been discussed in the context of allostery. However, the recent challenge to redesign K+-activated thrombin revealed that the allosteric interaction is insufficient to explain the mechanism. Under these circumstances, we have examined the roles of unbound Na+ molecule in maximization of thrombin-substrate association reaction rate. We performed all-atomic molecular dynamics (MD) simulations of thrombin in the presence of three different cations; Li+, Na+, and Cs+. Although these cations are commonly observed in the vicinity of the S1-pocket of thrombin, smaller cations are distributed more densely and extensively than larger ones. This suggests the two observation rules: (i) thrombin surrounded by Na+ is at an advantage in the initial step of association reaction, namely, the formation of an encounter complex ensemble, and (ii) the presence of Na+ molecules does not necessarily have an advantage in the final step of association reaction, namely, the formation of the stereospecific complex. In conclusion, we propose a conjecture that unbound Na+ molecules also affect the maximization of rate constant of thrombin-substrate association reaction through optimally forming an encounter complex ensemble.

Original languageEnglish
Pages (from-to)3635-3642
Number of pages8
JournalJournal of Physical Chemistry B
Volume119
Issue number9
DOIs
Publication statusPublished - 2015 Mar 5
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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