Molecular docking and in silico studies on analogues of 2-methylheptyl isonicotinate with DHDPS enzyme of Mycobacterium tuberculosis

  title={Molecular docking and in silico studies on analogues of 2-methylheptyl isonicotinate with DHDPS enzyme of Mycobacterium tuberculosis},
  author={Salam Pradeep Singh and Bolin Kumar Konwar and Rajib Lochan Bezbaruah and Tarun Chandra Bora},
  journal={Medicinal Chemistry Research},
Mycobacterium tuberculosis and other strains of mycobacteria cause tuberculosis which has infected one-third of the world’s population. Moreover, there has been increase in multidrug-resistant strains which spotlights the need for a new anti-tuberculosis drug. The cell wall of mycobacteria is characterised by high diaminopimelic acid (DAP) content—an intermediate of the (S)-lysine biosynthetic pathway and dihydrodipicolinate synthase (DHDPS) enzyme catalyses the first unique reaction of this… 
Hybrid Pharmacophore Approach as a Novel Strategy to identify Anti-Mycobacterial Chemotypes: Investigation with DapB Enzyme
Systematic analyses of structures, physicochemical/ADMET properties and molecular docking of the 387 and 982 compounds screened by the DHPM and conventional models respectively demonstrate the capabilities of DHPM to screen structurally diverse chemical entities with better druglike properties and higher target binding potentials.
Antimycobacterial activity of linoleic acid and oleic acid obtained from the hexane extract of the seeds of Mesua ferrea L. and their in silico investigation
The fatty acids- linoleic and oleic acids isolated and identified from the seeds of the plant Mesua ferrea L exhibited antimycobacterial activity and Cytotoxicity studies of the compounds revealed no toxicity and high antioxidant activity was observed.
Hybrid Dynamic Pharmacophore Models as Effective Tools to Identify Novel Chemotypes for Anti-TB Inhibitor Design: A Case Study With Mtb-DapB
Molecules screened by DHPM exhibited significant structural diversity, better binding strength and drug like properties as compared to the compounds screened by CPMs indicating the efficiency of DHPM to explore new chemical space for anti-TB drug discovery.


Virtual Screening of potential drug-like inhibitors against Lysine/DAP pathway of Mycobacterium tuberculosis
These novel scaffolds/candidates which could have the potential to inhibit Mtb DHDPS enzyme would represent promising starting points as lead compounds and certainly aid the experimental designing of antituberculars in lesser time.
Synthesis, absolute stereochemistry and molecular design of the new antifungal and antibacterial antibiotic produced by Streptomyces sp.201.
Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus anthracis at 1.94 Å resolution
The crystal structure of DHDPS from B. anthracis is reported, the first structure of a dihydrodipicolinate synthase from a Gram-positive bacterium.
Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis.
The three-dimensional structure of the enzyme dihydrodipicolinate synthase from Mycobacterium tuberculosis (Mtb-DHDPS) was determined and refined, which shows that the (S)-lysine-binding site is not conserved in Mtb, when compared with DHDPS enzymes that are known to be inhibited by (S-lysine).
Biosynthesis of diaminopimelate, the precursor of lysine and a component of peptidoglycan, is an essential function of Mycobacterium smegmatis
The evidence presented here indicates that the aspartate pathway is essential to M. smegmatis and that DAP is the essential product of this pathway.
Escherichia coli dihydrodipicolinate synthase. Identification of the active site and crystallization.
DHDPS catalyses the condensation of pyruvate and aspartate beta-semialdehyde by a ping-pong mechanism, and the density of the crystals indicates the presence of a dimer of DHDPS subunits per asymmetric unit.
Purification, crystallization and preliminary X-ray diffraction studies to near-atomic resolution of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus.
The structure of the enzyme will help to guide the design of novel therapeutics against the methicillin-resistant S. aureus pathogen.
Bacterial diaminopimelate metabolism as a target for antibiotic design.