The stereoinversion of amino acid residues in proteins is considered to trigger various age-related diseases. Serine (Ser) residues are relatively prone to stereoinversion. It is assumed that threonine (Thr) residues also undergo stereoinversion, which results in the formation of the d--Thr residue, by the same mechanisms as those for Ser-residue stereoinversion; however, d--Thr residues have not been detected in vivo. To date, although Ser-residue stereoinversion has been suggested to progress via enolization, plausible reaction mechanisms for Thr-residue stereoinversion have not been proposed. In this study, we investigated the pathway of Thr-residue enolization and successfully identified the three types of plausible reaction pathways of Thr-residue stereoinversion catalyzed by a dihydrogen phosphate ion. The geometries of reactant complexes, transition states, and enolized product complexes were optimized using B3LYP density functional methods, and single-point calculations were performed for all optimized geometries using Møller-Plesset perturbation theory to obtain reliable energies. As a result, the calculated activation energies of Thr-residue stereoinversion were 105-106 kJ mol, which were comparable with those of Ser-residue stereoinversion reported previously. The infrequency of Thr-residue stereoinversion may be due to other factors, such as the hydrophobicity and/or the steric hindrance of the γ-methyl group, rather than the high activation energies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178615PMC
http://dx.doi.org/10.1021/acsomega.2c00372DOI Listing

Publication Analysis

Top Keywords

thr-residue stereoinversion
16
ser-residue stereoinversion
12
stereoinversion
11
reaction mechanisms
8
stereoinversion catalyzed
8
catalyzed dihydrogen
8
dihydrogen phosphate
8
phosphate ion
8
plausible reaction
8
activation energies
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!