Free energy landscapes of prototropic tautomerism in pyridoxal 5'-phosphate schiff bases at the active site of an enzyme in aqueous medium

Journal of Computational Chemistry
Kumari Soniya, Amalendu Chandra

Abstract

We have performed hybrid quantum-classical metadynamics simulations and quantum chemical calculations to investigate the free energy landscapes of intramolecular proton transfer and associated tautomeric equilibrium in pyridoxal 5 '-phosphate (PLP) Schiff Bases, namely the internal and external aldimines, at the active site of serine hydroxymethyltransferase (SHMT) enzyme in aqueous medium. It is important to determine the relative stability of the two tautomers (ketoenamine and enolimine) of the PLP aldimines to study the catalytic activity of the concerned enzyme. Both the internal PLP aldimine (PLP-LYS) and the external PLP aldimine (PLP-SER) of SHMT are found to have a higher stability for the ketoenamine tautomer over the enolimine form. The higher stability of the ketoenamine tautomer can be attributed to the more number of favorable interactions of the ketoenamine form with its surroundings at the active site of the enzyme. The ketoenamine is found to be stabilized by about 2.5 kcal/mol in the PLP-LYS internal aldimine, while this stabilization is about 6.7 kcal/mol for the PLP-SER external aldimine at the active site of the enzyme compared to the corresponding enolimine forms. The interactions faced by the PLP aldimines...Continue Reading

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Citations

Oct 10, 2020·Molecular Microbiology·Michael D PaxhiaDiana M Downs
Aug 29, 2020·Journal of Chemical Theory and Computation·Emanuele GrifoniMichele Parrinello
Dec 14, 2018·The Journal of Physical Chemistry. B·Jirapat SantatiwongchaiM Paul Gleeson

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