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Na+ binding to meizothrombin desF1

M E Papaconstantinou1, P S Gandhi, Z Chen

  • 1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Cellular and Molecular Life Sciences : CMLS
|October 16, 2008
PubMed

Insights

This study reveals the first X-ray crystal structure of human meizothrombin, identifying a sodium (Na+) binding site similar to thrombin. This finding supports meizothrombin

Area of Science:

  • Biochemistry
  • Structural Biology
  • Enzymology

Background:

  • Meizothrombin is the active intermediate of prothrombin, crucial for blood coagulation.
  • Emerging evidence suggests meizothrombin functions as a sodium (Na+)-activated enzyme, similar to thrombin.

Purpose of the Study:

  • To determine the first X-ray crystal structure of human meizothrombin desF1.
  • To investigate the structural basis and functional implications of Na+ activation in meizothrombin.

Main Methods:

  • X-ray crystallography of human meizothrombin desF1 complexed with PPACK at 2.1 A resolution.
  • Stopped-flow fluorescence measurements to analyze Na+ binding kinetics.

Main Results:

  • The crystal structure revealed a Na+ binding site architecturally identical to that of human thrombin.
  • Kinetic studies demonstrated a slow phase of Na+ binding, indicative of multiple conformational states in equilibrium (E*, E, and E:Na+).

Conclusions:

  • Meizothrombin desF1 possesses a Na+ binding site structurally conserved with thrombin.
  • The existence of multiple conformations in meizothrombin provides critical insights into the prothrombin activation pathway.

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