Conformational features of lactate dehydrogenase: Temperature effect in presence of small molecules, mathematical model

The aim. To study the conformational changes of lactate dehydrogenase under the influence of different concentrations of intermediates (pyruvate, oxaloacetate) in the temperature gradient with the subsequent building of a mathematical model. Materials and methods. Thermolability of lactate dehydrogenase was studied using the method of differential scanning fluorimetry to determine the change in endogenous fluorescence of tryptophan and tyrosine under the conditions of stable concentration of lactate dehydrogenase and changing concentrations of pyruvate and oxaloacetate. Further, a mathematical model was developed for a more in-depth consideration of the behavior of the catalytic protein. Results. We found that pyruvate and oxaloacetate in low concentrations have a thermostabilizing effect on lactate dehydrogenase conformation; the effect of pyruvate is statistically more significant in comparison with oxaloacetate (p < 0.05). The studied ligands in high concentrations reduce the thermal stability of lactate dehydrogenase. Conclusion. Understanding the role of small molecules in the regulation of biological and catalytic processes has long remained in the background of scientific interest, but today the work in this direction is reaching a new level. The data obtained indicate the possibility of small molecules acting as ligands when interacting with enzymes. © 2020 Siberian State Medical University. All rights reserved.

Gilmiyarova Frida N. , Kuzmicheva Valeria K. , Kolotyeva Natalia A. , Komarova Marina V. , Ryskina Elena A. , Gusyakova Oksana A. , Vinogradova Daria S. , Salmin Vladimir V.
Siberian State Medical University
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  • 1 Samara State Medical University, 89, Chapayevskaya Str., Samara, 443099, Russian Federation
  • 2 Samara National Research University, 34, Moscow Highway, Samara, 443086, Russian Federation
  • 3 Peoples Friendship University of Russia, 6, Miklukho-Maklaya Str., Moscow, 117198, Russian Federation
  • 4 Petersburg Nucl. Phys. Inst. Named after B.P. Konstantinov of Natl. Res. Centre Kurchatov Institute, 1, Mkr. Orlova Roscha, Gatchina, Leningradskaya Oblast, 188300, Russian Federation
  • 5 Krasnoyarsk State Medical University Named after Professor V.F. Voino-Yasenetsky, 1, Partizana Zeleznyaka Str., Krasnoyarsk, 660022, Russian Federation
Ключевые слова
Conformation; Differential scanning fluorimetry; Lactate dehydrogenase; Oxaloacetate; Pyruvate
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