Thermal activation of 'allosteric-like' large-scale motions in a eukaryotic Lactate Dehydrogenase.

Abstract : Conformational changes occurring during the enzymatic turnover are essential for the regulation of protein functionality. Individuating the protein regions involved in these changes and the associated mechanical modes is still a challenge at both experimental and theoretical levels. We present here a detailed investigation of the thermal activation of the functional modes and conformational changes in a eukaryotic Lactate Dehydrogenase enzyme (LDH). Neutron Spin Echo spectroscopy and Molecular Dynamics simulations were used to uncover the characteristic length- and timescales of the LDH nanoscale motions in the apo state. The modes involving the catalytic loop and the mobile region around the binding site are activated at room temperature, and match the allosteric reorganisation of bacterial LDHs. In a temperature window of about 15 degrees, these modes render the protein flexible enough and capable of reorganising the active site toward reactive configurations. On the other hand an excess of thermal excitation leads to the distortion of the protein matrix with a possible anti-catalytic effect. Thus, the temperature activates eukaryotic LDHs via the same conformational changes observed in the allosteric bacterial LDHs. Our investigation provides an extended molecular picture of eukaryotic LDH's conformational landscape that enriches the static view based on crystallographic studies alone.
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Article dans une revue
Scientific Reports, Nature Publishing Group, 2017, 7, pp.41092
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http://hal.univ-grenoble-alpes.fr/hal-01480073
Contributeur : Frank Thomas <>
Soumis le : mercredi 1 mars 2017 - 09:46:10
Dernière modification le : lundi 19 février 2018 - 14:34:04

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  • HAL Id : hal-01480073, version 1
  • PUBMED : 28112231

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Marina Katava, Marco Maccarini, Guillaume Villain, Alessandro Paciaroni, Michael Sztucki, et al.. Thermal activation of 'allosteric-like' large-scale motions in a eukaryotic Lactate Dehydrogenase.. Scientific Reports, Nature Publishing Group, 2017, 7, pp.41092. 〈hal-01480073〉

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