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

Ikuo Kurisaki, Masataka Nagaoka*


研究成果: Article査読

3 被引用数 (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.

ジャーナルJournal of Physical Chemistry B
出版ステータスPublished - 2016 11月 23

ASJC Scopus subject areas

  • 物理化学および理論化学
  • 表面、皮膜および薄膜
  • 材料化学


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