TY - JOUR
T1 - An Artificial Heme Enzyme for Cyclopropanation Reactions
AU - Villarino, Lara
AU - Splan, Kathryn E.
AU - Reddem, Eswar
AU - Alonso-Cotchico, Lur
AU - Gutiérrez de Souza, Cora
AU - Lledós, Agustí
AU - Maréchal, Jean Didier
AU - Thunnissen, Andy Mark W.H.
AU - Roelfes, Gerard
PY - 2018/6/25
Y1 - 2018/6/25
N2 - © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.
AB - © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.
KW - artificial metalloenzymes
KW - biocatalysis
KW - carbenes
KW - enzyme design
KW - heme enzymes
U2 - https://doi.org/10.1002/anie.201802946
DO - https://doi.org/10.1002/anie.201802946
M3 - Article
VL - 57
SP - 7785
EP - 7789
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 26
ER -