title: Targeting PknB, an eukaryotic-like serine/threonine protein kinase of Mycobacterium tuberculosis with phytomolecules.
abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis is one of the most lethal communicable disease globally. As per the WHO Global TB Report (2015), 9.6 million cases were reported in year 2014 alone. The receptor-like protein kinase, PknB is crucial for sustained mycobacterial growth. Therefore, PknB can be a potential target to develop anti-tuberculosis drugs. In present study, we performed a comparative study to investigate binding efficacies of three phytomolecules namely, Demethylcalabaxanthone, Cryptolepine hydrochloride and Ermanin. 3D structures of PknB and phytomolecules were retrieved from Protein Data Bank (PDB ID: 2FUM) and PubChem Chemical Compound Database, respectively. PknB was set to be rigid and phytochemicals were kept free to rotate. All computational simulations were carried out using Autodock 4.0 on Windows platform. In-silico study demonstrated a strong complex formation (large binding constants and low ΔG) between phytomolecules and target protein PknB of Mycobacterium tuberculosis. However, Demethylcalabaxanthone was able to bind PknB more strongly (Kb=6.8×105M-1, ΔG=-8.06kcal/mol) than Cryptolepine hydrochloride (Kb=3.06×105M-1, ΔG=-7.58kcal/mol) and Ermanin (Kb=9.8×104M-1, ΔG=-6.9kcal/mol). These in silico analysis indicate that phytomolecules are capable to target PknB protein efficiently which is vital for mycobacterial survival and therefore can be excellent alternatives to conventional anti-tuberculosis drugs.
authors.affiliation: Dept. of Biochemistry, Malabar Medical College Hospital & Research Centre, Kerala, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Appunni
authors.affiliation: Dept. of Physical Medicine and Rehabilitation, Government Medical College, Kerala, India.
authors.forename: P M
authors.initials: PM
authors.lastname: Rajisha
authors.affiliation: Dept. of Health Promotion & Disease Prevention, Florida International University, FL, USA.
authors.forename: Muni
authors.initials: M
authors.lastname: Rubens
authors.affiliation: Bioinformatics Division, MTA Infotech, Varanasi, UP, India.
authors.forename: Sangoju
authors.initials: S
authors.lastname: Chandana
authors.affiliation: School of Sciences, Noida International University, Greater Noida, India. Electronic address: himanshu720@gmail.com.
authors.forename: Himanshu Narayan
authors.initials: HN
authors.lastname: Singh
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: vishnuswarup@gmail.com.
authors.forename: Vishnu
authors.initials: V
authors.lastname: Swarup
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry; D026121:Indole Alkaloids / Q000737:chemistry; D008024:Ligands; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry; D044004:Xanthones / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D005419:Flavonoids; D026121:Indole Alkaloids; D008024:Ligands; D011804:Quinolines; D044004:Xanthones; C104804:ermanin; C024015:cryptolepine; C475060:PknB protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases
keywords: Mycobacterium tuberculosis; Phytomolecules; PknB; Serine/threonine protein kinases