The Translocation of Na+ Ion Inside Human Thrombin Accounts for the Activation of the Enzyme

Hagit Gdalya, Esther Nachliel, Menachem Gutman, Yulia Einav*, Yossi Tsfadia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Thrombin is a member of the chymotrypsin family that splits the peptide bond next to arginine. The catalytic activity of thrombin is accelerated by Na+. Inspection of the crystal structure reveals an ion binding site 17 Å from the active-site, leading to ambiguous definition of its mode of rate-enhancement. During unbiased Molecular Dynamics simulations in the presence of Na+ ions, the Na+ ion was noticed to alternate between two locations: the crystal-structure site (adjacent to R221a and K224) and another site next to D189, very close to the binding and the active sites. There is a free passage between the two locations, and both sites can exchange ions with the bulk. When the ion is close to D189 it can assume position between the guanidino moiety of the product and the carboxylate of D189, thus weakening the protein-product interaction. This transient structure either ejects the Na+ ion out of the protein or releases the product from the enzyme. We propose that the enhancement of the catalysis by the ion is a reflection of its ability to destabilize the product-enzyme complex.

Original languageEnglish
Pages (from-to)413-423
Number of pages11
JournalIsrael Journal of Chemistry
Issue number5
StatePublished - 1 May 2017


  • Allosteric activation
  • Molecular Dynamics
  • Na binding sites
  • Thrombin.
  • enzyme catalysis


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