Peptide Bond Formation Mechanism Catalyzed by Ribosome.
In this paper we present a study of the peptide bond formation reaction catalyzed by ribosome. Different mechanistic proposals have been explored by means of Free Energy Perturbation methods within hybrid QM/MM potentials, where the chemical system has been described by the M06-2X functional and the environment by means of the AMBER force field. According to our results, the most favorable mechanism in the ribosome would proceed through an eight-membered ring transition state, involving a proton shuttle mechanism through the hydroxyl group of the sugar and a water molecule. This transition state is similar to that described for the reaction in solution (J. Am. Chem. Soc. 2013, 135, 8708-8719), but the reaction mechanisms are noticeably different. Our simulations reproduce the experimentally determined catalytic effect of ribosome that can be explained by the different behavior of the two environments. While the solvent reorganizes during the chemical process involving an entropic penalty, the ribosome is preorganized in the formation of the Michaelis complex and does not suffer important changes along the reaction, dampening the charge redistribution of the chemical system.
Departament de Química Física i Analítica, Universitat Jaume I , 12071 Castellón Spain.|Institute of Applied Radiation Chemistry, Lodz University of Technology , 90-924 Lodz, Poland.
Katarzyna
K
Świderek
Departament de Química Física i Analítica, Universitat Jaume I , 12071 Castellón Spain.
Sergio
S
Marti
Departament de Química Física, Universitat de València , 46100 Burjasot, Spain.
Iñaki
I
Tuñón
Departament de Química Física i Analítica, Universitat Jaume I , 12071 Castellón Spain.
Vicent
V
Moliner
Departament de Química, Universitat Autònoma de Barcelona , 08193 Bellaterra, Spain.
Juan
J
Bertran
D055162:Biocatalysis; D004583:Electrons; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D012270:Ribosomes / Q000378:metabolism*; D013816:Thermodynamics
D010455:Peptides