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Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.49 [2012] >
IJBB Vol.49(3) [June 2012] >
| Title: | 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 |
| Authors: | Chakrabarty, Kuheli
Gupta, Sampad Narayan
Das, Gourab Kanti
Roy, Sukhendu |
| Keywords: | Enzyme
Molecular dynamics
Quantum mechanics
Density functional theory
Pyridoxal-5'-phosphate
Carbidopa
Decarboxylase, Aldimine |
| Issue Date: | Jun-2012 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | 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 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. |
| Page(s): | 155-164 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.49(3) [June 2012]
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