Changeover from (3,4) ene cyclization to (3,5) mode under the influence of Lewis acid catalyst: A quantum mechanical study

1637-1644Transition structures (TSs) for the Lewis acid catalyzed ene cyclization reaction have been optimized quantum mechanically and the selectivity for the (3,5) ene cyclized product have been compared with that of (3,4) product. Analysis of the result shows that the geometric deformation of the TS produced due to the presence of Lewis acid in the environment plays a significant role in determining the selectivity of (3,5) ene product. This geometric deformation originates from the enlarged dihedral angle around the forming carbon-carbon bond in the Lewis acid catalyzed TS

Theoretical studies on the pyridoxal-5'-phosphate dependent enzyme dopa decarboxylase: Effect of Thr 246 residue on the co-factor-enzyme binding and reaction mechanism

155-164Decarboxylation of amino acid is a key step for biosynthesis of several important cellular metabolites in the biological systems. This process is catalyzed by amino acid decarboxylases and most of them use pyridoxal-5'-phosphate (PLP) as a co-factor. PLP is bound to the active site of the enzyme by various interactions with the neighboring amino acid residues. In the present investigation, density functional theory (DFT) and real-time dynamics studies on both ligand-free and ligand-bound dopa decarboxylases (DDC) have been carried out in order to elucidate the factors responsible for facile decarboxylation and also for proper binding of PLP in the active site of the enzyme. It has been found that in the crystal structure Asp271 interacts with the pyridine nitrogen atom of PLP through H-bonding in both native and substrate-bound DDC. On the contrary, Thr246 is in close proximity to the oxygen of 3-OH of PLP pyridine ring only in the substrate-bound DDC. In the ligand-free enzyme, the distance between the oxygen atom of 3-OH group of PLP pyridine ring and oxygen atom of Thr246 hydroxyl group is not favorable for hydrogen bonding. Thus, present study reveals that hydrogen bonding with O3 of PLP with a hydrogen bond donor residue provided by the enzyme plays an important role in the decarboxylation process