Contribution of a single hydroxyl group to transition-state discrimination by adenosine deaminase: evidence for an "entropy trap" mechanism

Biochemistry ◽  
1989 ◽  
Vol 28 (19) ◽  
pp. 7919-7927 ◽  
Author(s):  
Warren M. Kati ◽  
Richard Wolfenden
Keyword(s):  
Transition State ◽  
Adenosine Deaminase ◽  
Hydroxyl Group ◽  
State Discrimination

Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase

Biochemistry ◽  
1995 ◽  
Vol 34 (14) ◽  
pp. 4516-4523 ◽  
Author(s):  
Shibin Xiang ◽  
Steven A. Short ◽  
Richard Wolfenden ◽  
Charles W. Carter
Keyword(s):  
Transition State ◽  
Cytidine Deaminase ◽  
Hydroxyl Group ◽  
State Selectivity

The Role of the 5'-Hydroxyl Group of Adenosine in Determining Substrate Specificity for Adenosine Deaminase

1967 ◽  
Vol 10 (5) ◽  
pp. 908-912 ◽  
Author(s):  
Alexander. Bloch ◽  
Morris J. Robins ◽  
James R. McCarthy
Keyword(s):  
Substrate Specificity ◽  
Adenosine Deaminase ◽  
Hydroxyl Group

A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

Biochemistry ◽  
1992 ◽  
Vol 31 (32) ◽  
pp. 7356-7366 ◽  
Author(s):  
Warren M. Kati ◽  
Scott A. Acheson ◽  
Richard Wolfenden
Keyword(s):  
Ligand Binding ◽  
Transition State ◽  
Adenosine Deaminase ◽  
Entropic Effects

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.

Sign in / Sign up

Export Citation Format

Share Document