Minimal Transition State Charge Stabilization of the Oxyanion during Peptide Bond Formation by the Ribosome

Biochemistry ◽  
2011 ◽  
Vol 50 (48) ◽  
pp. 10491-10498 ◽  
Author(s):  
Nicolas Carrasco ◽  
David A. Hiller ◽  
Scott A. Strobel
Keyword(s):  
Transition State ◽  
Bond Formation ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
State Charge ◽  
Charge Stabilization

scholarly journals The transition state for peptide bond formation reveals the ribosome as a water trap

2010 ◽  
Vol 107 (5) ◽  
pp. 1888-1893 ◽  
Author(s):  
Göran Wallin ◽  
Johan Åqvist
Keyword(s):  
Water Molecule ◽  
Transition State ◽  
Activation Enthalpy ◽  
Molecular Model ◽  
Isotope Effects ◽  
Bond Formation ◽  
Transition States ◽  
Peptide Bond ◽  
Hydroxyl Group ◽  
Peptide Bond Formation

Recent progress in elucidating the peptide bond formation process on the ribosome has led to notion of a proton shuttle mechanism where the 2'-hydroxyl group of the P-site tRNA plays a key role in mediating proton transfer between the nucleophile and leaving group, whereas ribosomal groups do not actively participate in the reaction. Despite these advances, the detailed nature of the transition state for peptidyl transfer and the role of several trapped water molecules in the peptidyl transferase center remain major open questions. Here, we employ high-level quantum chemical ab initio calculations to locate and characterize global transition states for the reaction, described by a molecular model encompassing all the key elements of the reaction center. The calculated activation enthalpy as well as structures are in excellent agreement with experimental data and point to feasibility of an eight-membered “double proton shuttle” mechanism in which an auxiliary water molecule, observed both in computer simulations and crystal structures, actively participates. A second conserved water molecule is found to be of key importance for stabilizing developing negative charge on the substrate oxyanion and its presence is catalytically favorable both in terms of activation enthalpy and entropy. Transition states calculated both for six- and eight-membered mechanisms are invariably late and do not involve significant charge development on the attacking amino group. Predicted kinetic isotope effects consistent with this picture are similar to those observed for uncatalyzed ester aminolysis reactions in solution.

Quantum Transition State for Peptide Bond Formation in the Ribosome

2010 ◽  
pp. 499-515 ◽  
Author(s):  
Lou Massa ◽  
Chérif F. Matta ◽  
Ada Yonath ◽  
Jerome Karle
Keyword(s):  
Transition State ◽  
Bond Formation ◽  
Peptide Bond ◽  
Quantum Transition ◽  
Peptide Bond Formation

Beyond peptide bond formation: the versatile role of condensation domains in natural product biosynthesis

2021 ◽  
Author(s):  
Sofie Dekimpe ◽  
Joleen Masschelein
Keyword(s):  
Natural Product ◽  
Bond Formation ◽  
Peptide Bond ◽  
Chemical Diversity ◽  
Peptide Bond Formation ◽  
Natural Product Biosynthesis

Condensation domains perform highly diverse functions during natural product biosynthesis and are capable of generating remarkable chemical diversity.

scholarly journals En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal–Organic Framework Catalysts

ACS Catalysis ◽  
2021 ◽  
pp. 7647-7658
Author(s):  
Francisco de Azambuja ◽  
Alexandra Loosen ◽  
Dragan Conic ◽  
Maxime van den Besselaar ◽  
Jeremy N. Harvey ◽  
...  
Keyword(s):  
Metal Organic Framework ◽  
Bond Formation ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
Heterogeneous Catalytic ◽  
Metal Organic ◽  
Organic Framework
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