TY - JOUR
T1 - Efficient Encounter Complex Formation and Electron Transfer to Cytochrome c Peroxidase with an Additional, Distant Electrostatic Binding Site
AU - Di Savino, Antonella
AU - Foerster, Johannes M.
AU - La Haye, Thijmen
AU - Blok, Anneloes
AU - Timmer, Monika
AU - Ullmann, G. Matthias
AU - Ubbink, Marcellus
PY - 2020
Y1 - 2020
N2 - Electrostatic interactions can strongly increase the efficiency of protein complex formation. The charge distribution in redox proteins is often optimized to steer a redox partner to the electron transfer active binding site. To test whether the optimized distribution is more important than the strength of the electrostatic interactions, an additional negative patch was introduced on the surface of cytochrome c peroxidase, away from the stereospecific binding site, and its effect on the encounter complex as well as the rate of complex formation was determined. Monte Carlo simulations and paramagnetic relaxation enhancement NMR experiments indicate that the partner, cytochrome c, interacts with the new patch. Unexpectedly, the rate of the active complex formation was not reduced, but rather slightly increased. The findings support the idea that for efficient protein complex formation the strength of the electrostatic interaction is more critical than an optimized charge distribution.
AB - Electrostatic interactions can strongly increase the efficiency of protein complex formation. The charge distribution in redox proteins is often optimized to steer a redox partner to the electron transfer active binding site. To test whether the optimized distribution is more important than the strength of the electrostatic interactions, an additional negative patch was introduced on the surface of cytochrome c peroxidase, away from the stereospecific binding site, and its effect on the encounter complex as well as the rate of complex formation was determined. Monte Carlo simulations and paramagnetic relaxation enhancement NMR experiments indicate that the partner, cytochrome c, interacts with the new patch. Unexpectedly, the rate of the active complex formation was not reduced, but rather slightly increased. The findings support the idea that for efficient protein complex formation the strength of the electrostatic interaction is more critical than an optimized charge distribution.
KW - electrostatic interactions
KW - encounter complexes
KW - NMR spectroscopy
KW - paramagnetic relaxation enhancement
KW - protein–protein interactions
UR - http://www.scopus.com/inward/record.url?scp=85092394089&partnerID=8YFLogxK
U2 - 10.1002/anie.202010006
DO - 10.1002/anie.202010006
M3 - Article
AN - SCOPUS:85092394089
SN - 1433-7851
VL - 59
SP - 23239
EP - 23243
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 51
ER -