TY  - JOUR
AU  - Katava, Marina
AU  - Maccarini, Marco
AU  - Villain, Guillaume
AU  - Paciaroni, Alessandro
AU  - Sztucki, Michael
AU  - Ivanova, Oxana
AU  - Madern, Dominique
AU  - Sterpone, Fabio
TI  - Thermal activation of ‘allosteric-like’ large-scale motions in a eukaryotic Lactate Dehydrogenase
JO  - Scientific reports
VL  - 7
SN  - 2045-2322
CY  - London
PB  - Nature Publishing Group
M1  - FZJ-2017-01459
SP  - 41092 -
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000392465800001
DO  - DOI:10.1038/srep41092
UR  - https://juser.fz-juelich.de/record/827265
ER  -