Abstract
Pyridoxal Kinase (PLK) phosphorylates vitamin B6, a step required for the conversion of Vitamin B6 into pyridoxal 5-phosphate. The protein is cytoplasmic and is active as a dimer. Molecular dynamics (MD) simulation studies using a 25ns scale for PLK and its complex with ATP (Adenosine triphosphate) and ADP (Adenosine diphosphate) were carried out and the trajectory analysis revealed that the flexibility of the entire PLK molecule increases. In present study we have investigated the conformational changes in pyridoxal kinase (PLK) after binding of ligands (ATP/ADP). The stability of native and PLK in complex with ATP and ADP, was ascertained by MD simulations and mechanism of ligand binding was explored by essential dynamics. Simulation results also indicated that the van der Waals contribution was greater than the electrostatic interaction between the protein residues and the ligands. Further, the ligand (ATP/ADP) binding results into decrement and increment of fluctuations in certain regions of protein.
Highlights
Pyridoxal kinase (PLK) is an enzyme belonging to ribokinase super-family that catalyzes the conversion of pyridoxal to pyridoxal 5’-phosphate (PLP).The two substrates of this enzyme are ATP and pyridoxal, whereas its two products are ADP and pyridoxal 5'-phosphate.PLP acts as an essential ubiquitous coenzyme in many aspects of amino acids and cellular metabolism such as transamination, decarboxylation, and synthesis pathways involving carbohydrates, sphingolipids, amino acids, heme and neurotransmitters [1]
We demonstrate that the molecular basis of Pyridoxal Kinase (PLK) function is largely determined by the mechanism in which, the ligand can modulate the conformational dynamics of PLK linked to the functional activities [8-9]
Molecular Dynamics simulations of the Pyridoxal Kinase complex with ATP (PLK+ATP) and the Pyridoxal kinase complexed with ADP (PLK+ADP) were performed using the explicit SPC water model by applying periodic boundary conditions
Summary
Pyridoxal kinase (PLK) is an enzyme belonging to ribokinase super-family that catalyzes the conversion of pyridoxal to pyridoxal 5’-phosphate (PLP).The two substrates of this enzyme are ATP and pyridoxal, whereas its two products are ADP and pyridoxal 5'-phosphate.PLP acts as an essential ubiquitous coenzyme in many aspects of amino acids and cellular metabolism such as transamination, decarboxylation, and synthesis pathways involving carbohydrates, sphingolipids, amino acids, heme and neurotransmitters [1]. In the presence of MgATP, PL kinase catalyzes the additionof phosphate to the 5’ alcohol of pyridoxine, pyridoxamine and PL to form pyridoxine 5’-phosphate, pyridoxamine 5’-phosphateand PLP, respectively [2]. The findings obtained are useful for revealing the conformational changes in PLK after binding of the ligands. Elucidation of the ligand binding mechanism is the necessary step to obtain more selective and potent drugs for this new potential target
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