Na+ binding is ineffective in forming a primary substrate pocket of thrombin

Ikuo Kurisaki, Masataka Nagaoka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Thrombin is a serine protease involved in the blood coagulation reaction, and it shows maximum enzymatic activity in the presence of Na+. It has been supposed that Na+ binding promotes conversion from the inactive form, with a collapsed primary substrate pocket (S1 pocket), to the active form, with a properly formed S1 pocket. However, the evidence supporting this activation mechanism was derived from the X-ray crystallographic structures solved under nonphysiological conditions and using thrombin mutants; thus, it still remains elusive whether the activation mechanism is actually attributed to Na+ binding. To address the problem, we employed all-atom molecular dynamics simulations for both active and inactive forms of thrombin in the presence and absence of Na+ binding and examined the effect of Na+ binding on S1-pocket formation. In contrast to the conventional supposition, we revealed that Na+ binding does not prevent S1-pocket collapse virtually, but rather, the bound Na+ can move to the S1 pocket, thus blocking substrate access directly. Additionally, it was clarified that Na+ binding does not promote S1-pocket formation. According to these insights, we concluded that Na+ binding is irrelevant to the interconversion between the inactive and active forms of thrombin.

Original languageEnglish
Pages (from-to)11873-11879
Number of pages7
JournalJournal of Physical Chemistry B
Issue number46
Publication statusPublished - 2016 Nov 23
Externally publishedYes

ASJC Scopus subject areas

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


Dive into the research topics of 'Na+ binding is ineffective in forming a primary substrate pocket of thrombin'. Together they form a unique fingerprint.

Cite this