European Biophysics Journal

, 37:1139 | Cite as

Adjustment of conformational flexibility of glyceraldehyde-3-phosphate dehydrogenase as a means of thermal adaptation and allosteric regulation

  • István Hajdú
  • Csaba Bőthe
  • András Szilágyi
  • József Kardos
  • Péter Gál
  • Péter Závodszky
Original Paper


Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Thermotoga maritima (TmGAPDH) is a thermostable enzyme (T m = 102°C), which is fully active at temperatures near 80°C but has very low activity at room temperature. In search for an explanation of this behavior, we measured the conformational flexibility of the protein by hydrogen–deuterium exchange and compared the results with those obtained with GAPDH from rabbit muscle (RmGAPDH). At room temperature, the conformational flexibility of TmGAPDH is much less than that of RmGAPDH, but increases with increasing temperature and becomes comparable to that of RmGAPDH near the physiological temperature of Thermotoga maritima. Using the available three-dimensional structures of the two enzymes, we compared the B factors that reflect the local mobility of protein atoms. The largest differences in B factors are seen in the coenzyme and NAD binding regions. The likely reason for the low activity of TmGAPDH at room temperature is that the motions required for enzyme functions are restricted. The findings support the idea of “corresponding states” which claims that over the time span of evolution, the overall conformational flexibility of proteins has been preserved at their corresponding physiological temperatures.


Conformational flexibility Thermal adaptation Protein stability Glyceraldehyde-3-phosphate dehydrogenase Allosteric regulation 



Péter Závodszky was supported by the Hungarian National Science Foundation (OTKA) Grants T046412, and NI-61915. A.S. was supported by a Bolyai János fellowship.


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Copyright information

© EBSA 2008

Authors and Affiliations

  • István Hajdú
    • 1
  • Csaba Bőthe
    • 1
  • András Szilágyi
    • 1
  • József Kardos
    • 1
    • 2
  • Péter Gál
    • 1
  • Péter Závodszky
    • 1
  1. 1.Institute of Enzymology, Biological Research CenterHungarian Academy of SciencesBudapestHungary
  2. 2.Department of BiochemistryEötvös Loránd UniversityBudapestHungary

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