skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Na[superscript +] binding to meizothrombin desF1

Abstract

Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na{sup +}-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 {angstrom} resolution. The structure reveals a Na{sup +} binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na{sup +} binding to meizothrombin desF1 document a slow phase of fluorescence change with a k obs decreasing hyperbolically with increasing [Na{sup +}], consistent with the existence of three conformations in equilibrium, E*, E and E:Na{sup +}, as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.

Authors:
; ; ; ;  [1]
  1. (WU-MED)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1007099
Resource Type:
Journal Article
Journal Name:
Cell Mol. Life Sci.
Additional Journal Information:
Journal Volume: 65; Journal Issue: (22) ; 11, 2008
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; ARCHITECTURE; CHAINS; CLEAVAGE; CRYSTAL STRUCTURE; FLUORESCENCE; PROTHROMBIN; RESOLUTION; THROMBIN

Citation Formats

Papaconstantinou, M.E., Gandhi, P.S., Chen, Z., Bah, A., and Di Cera, E.. Na[superscript +] binding to meizothrombin desF1. United States: N. p., 2009. Web. doi:10.1007/s00018-008-8502-7.
Papaconstantinou, M.E., Gandhi, P.S., Chen, Z., Bah, A., & Di Cera, E.. Na[superscript +] binding to meizothrombin desF1. United States. doi:10.1007/s00018-008-8502-7.
Papaconstantinou, M.E., Gandhi, P.S., Chen, Z., Bah, A., and Di Cera, E.. Wed . "Na[superscript +] binding to meizothrombin desF1". United States. doi:10.1007/s00018-008-8502-7.
@article{osti_1007099,
title = {Na[superscript +] binding to meizothrombin desF1},
author = {Papaconstantinou, M.E. and Gandhi, P.S. and Chen, Z. and Bah, A. and Di Cera, E.},
abstractNote = {Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na{sup +}-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 {angstrom} resolution. The structure reveals a Na{sup +} binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na{sup +} binding to meizothrombin desF1 document a slow phase of fluorescence change with a k obs decreasing hyperbolically with increasing [Na{sup +}], consistent with the existence of three conformations in equilibrium, E*, E and E:Na{sup +}, as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.},
doi = {10.1007/s00018-008-8502-7},
journal = {Cell Mol. Life Sci.},
number = (22) ; 11, 2008,
volume = 65,
place = {United States},
year = {2009},
month = {6}
}