Thermodynamics of Na+ binding to coagulation serine proteases.
The sodium binding to serine proteases triggers a conformational change in the proteins that enhances the catalytic activity of the enzymes. The interaction of the cation with the protein is mediated by the hydrogen-bonding network of water molecules that embed the Na+ site. We pointed out the crucial role of the insertion loop 186a-d and the I16-D194 ion pair in the stabilization of sodium binding pocket in thrombin. This paper contributes to better explain the molecular mechanism of sodium binding for different serine proteases leading to the identification of the structural changes necessary to engineer a functional Na+ site and regulate catalytic activity in serine proteases.
Griffon
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N
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Di Stasio
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E
D001777:Blood Coagulation / Q000502:physiology*; D002412:Cations / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D011485:Protein Binding; D011486:Protein C / Q000737:chemistry; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics; D013917:Thrombin / Q000737:chemistry; D014867:Water / Q000737:chemistry
D002412:Cations; D011486:Protein C; D014867:Water; D012964:Sodium; D012697:Serine Endopeptidases; D013917:Thrombin; D015951:Factor Xa