ABSTRACT
Burkholderia sp. strain USMB20 is a plant growth-promoting rhizobacterium that was isolated from nodules of the leguminous cover crop Mucuna bracteata. The draft genome sequence of Burkholderia sp. strain USMB20 has an assembly size of 7.7 Mbp in 26 contigs with a GC content of 66.88%.
ABSTRACT
The allosteric pocket of the Dengue virus (DENV2) NS2B/NS3 protease, which is proximal to its catalytic triad, represents a promising drug target (Othman et al., 2008). We have explored this binding site through large-scale virtual screening and molecular dynamics simulations followed by calculations of binding free energy. We propose two mechanisms for enzyme inhibition. A ligand may either destabilize electronic density or create steric effects relating to the catalytic triad residues NS3-HIS51, NS3-ASP75, and NS3-SER135. A ligand may also disrupt movement of the C-terminal of NS2B required for inter-conversion between the "open" and "closed" conformations. We found that chalcone and adenosine derivatives had the top potential for drug discovery hits, acting through both inhibitory mechanisms. Studying the molecular mechanisms of these compounds might be helpful in further investigations of the allosteric pocket and its potential for drug discovery.
Subject(s)
Allosteric Site , Dengue Virus/enzymology , Drug Evaluation, Preclinical , Molecular Dynamics Simulation , Protease Inhibitors/analysis , Serine Endopeptidases/metabolism , Dengue Virus/drug effects , Hydrogen Bonding , Ligands , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Structural Homology, Protein , ThermodynamicsABSTRACT
BACKGROUND: Hevea brasiliensis, a member of the Euphorbiaceae family, is the major commercial source of natural rubber (NR). NR is a latex polymer with high elasticity, flexibility, and resilience that has played a critical role in the world economy since 1876. RESULTS: Here, we report the draft genome sequence of H. brasiliensis. The assembly spans ~1.1 Gb of the estimated 2.15 Gb haploid genome. Overall, ~78% of the genome was identified as repetitive DNA. Gene prediction shows 68,955 gene models, of which 12.7% are unique to Hevea. Most of the key genes associated with rubber biosynthesis, rubberwood formation, disease resistance, and allergenicity have been identified. CONCLUSIONS: The knowledge gained from this genome sequence will aid in the future development of high-yielding clones to keep up with the ever increasing need for natural rubber.
