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.

Published

Journal Article

Decarboxylation 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 ofPLP 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 03 of PLP with a hydrogen bond donor residue provided by the enzyme plays an important role in the decarboxylation process.

Full Text

Duke Authors

Cited Authors

  • Chakrabarty, K; Gupta, SN; Das, GK; Roy, S

Published Date

  • June 2012

Published In

Volume / Issue

  • 49 / 3

Start / End Page

  • 155 - 164

PubMed ID

  • 22803330

Pubmed Central ID

  • 22803330

Electronic International Standard Serial Number (EISSN)

  • 0975-0959

International Standard Serial Number (ISSN)

  • 0301-1208

Language

  • eng