Molecular dynamic simulations of Escherichia coli L-asparaginase to illuminate its role in deamination of asparagine and glutamine residues.
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar®(L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar®with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified. For the apo state enzyme and ligand bound state complexes, MD simulations were performed. Trajectory analysis for 30 ns run confirmed the kinship of L-Asn with L-asparaginase enzyme in the dynamic system with less stability in comparison to L-Gln docked complex. Overall findings strongly supported the bi-functional nature of the enzyme drug. A good number of conformational changes were observed with 1NNS structure due to ligand binding. Results of present study give much more information on structural and functional aspects of E. coli L-asparaginase upon the interaction with its ligands which may be useful in designing effective therapeutics for ALL.
Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India. rajeshreddy.bio@gmail.com.
Rajeswara Reddy
http://orcid.org/0000-0001-9606-4989
RR
Erva
Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India.
Satish Babu
SB
Rajulapati
School of Information Technology, Jawaharlal Nehru Technological University Hyderabad, Hyderabad, 500085, Telangana, India.
Chandrasai
C
Potla Durthi
Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India.
Mayuri
M
Bhatia
Department of Biotechnology, National Institute of Technology Warangal, Warangal, 506004, Telangana, India.
Madhuri
M
Pola
Acute lymphocytic leukemia; L-asparaginase; Molecular docking; Molecular dynamic simulations