<i>Insilico</i> studies of 2-methylheptyl isonicotinate produced by <i>Streptomyces</i> sps. 201 against dihydrodipicolinate synthase enzyme of <i>Mycobacterium tuberculosis</i>
- 1 Bioinformatics Infrastructure Facility, Biotechnology Division, North-East Institute of Science & Technology, Jorhat, India
- 2 Bioinformatics Infrastructure Facility, Biotechnology Division, North-East Institute of Science & Technology, Jorhat, India
- 3 Bioinformatics Infrastructure Facility, Biotechnology Division, North-East Institute of Science & Technology, Jorhat, India
Abstract
Tuberculosis is thought to have infected one-third of the world’s population and antibiotic resistance is a growing problem in multi-drug-resistant tuberculosis which is caused by Mycobacterium tuberculosis (MTB). It has been reported that Mycobacterial cell walls are characterized by high DAP (diaminopimelic acid) content—an intermediate of the (S)-lysine biosynthetic pathway. Hence, the Lysine/DAP biosynthetic pathway is a promising target because of its role in cell wall and amino acid biosynthesis. In this study we performed a molecular docking analysis of a novel antibacterial isolated from Streptomyces sps. 201 against dihydrodipicolinate synthase (DHDPS) enzyme of Mycobacterium tuberculosis . The docking studies suggest that the novel molecule binds at active site LYS 171 forming a cleft and at other potential ligand binding site exhibiting all the major interactions such as hydrogen bonding, hydrophobic interaction and electrostatic interaction with (THR55, TYR143, ARG148, LYS171, VAL257 and GLY256) residues.
- Kumar, V., Abbas, A.K., Fausto, N. and Mitchell, R.N. (2007) Robbins basic pathology (8th Edtion). Saunders Elsevier, 516-522.
- Jasmer, R.M., Nahid, P., Hopewell P.C. (2002) Clinical practice. Latent tuberculosis infection. The New England Journal of Medicine, 347, 1860-1866. doi:10.1056/NEJMcp021045
- World Health Organization (2007) Tuberculosis. http://who.int/mediacentre/factsheets/fs104/en/index.html
- World Health Organization (2009) Global tuberculosis control: epidemiology, strategy, financing. Epidemiology, 6-33. http://who.int/entity/tb/publications/global_report/2009/pdf/chapter1.pdf
- Kefala, G., Evans, G.L., Griffin, M.D., Devenish, S.R., Pearce, F.G., Perugini, M.A., Gerrard J.A., Weiss, M.S. and Dobson, R.C. (2008) Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis. Biochemical Journal, 411, 351-360. doi:10.1042/BJ20071360
- Turner, J.J., Gerrard, J.A. and Hutton, C.A. (2005) Heterocyclic inhibitors of dihydrodipicolinate synthase are not competitive. Bioorganic & Medicinal Chemistry, 13, 2133-2140. doi:10.1016/j.bmc.2005.01.001
- Turner, J.J., Healy, J.P., Dobson, R.C., Gerrard, J.A. and Hutton, C.A. (2005) Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl(E,E)-4-oxo-2,5-heptadiene-dioate and diethyl(E)-4-oxo-2-heptenedioate. Bioorganic & Medicinal Chemistry, 15, 995-998. doi:10.1016/j.bmcl.2004.12.043
- Turner, J.J., Gerrard, J.A. and Hutton, C.A. (2005) Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase. Bioorganic & Medicinal Chemistry, 13, 2133-2140. doi:10.1016/j.bmc.2005.01.001
- Bordoloi, G.N., Babita, K., Arijit, G., Manobjyoti, B., Yadav, R.N.S., Manoj, K.R. and Bora, T.C. (2001) Isolation and structure elucidation of a new antifungal and antibacterial antibiotic produced by Streptomycin sp. 201. Bioscience, Biotechnology, and Biochemistry, 65, 1856-1858.
- Bordoloi, G., Kumari, B., Bordoloi, M., Roy, M.K. and Bora, T.C. (2001) A process for the production of 2-methyl-heptyl isonicotinate. Indian Patent NF-9/2000.
- Bordoloi, G., Kumari, B., Bordoloi, M., Roy, M.K. and Bora, T.C. (2000) 2-Methylheptyl isonicotinate as novel antibiotic. Indian Patent NF-116/2001.
- Bordoloi, G., Kumari, B., Bordoloi, M., Roy, M.K., Bora, T.C. (2000) A process for the production of 2-methylheptyl isonicotinate. US Patent 009 NF 2000, 10/027913.