Structural analysis and molecular docking of potential ligands with chorismate synthase of Listeria monocytogenes: A novel antibacterial drug target.

Listeriosis, in particular that caused by Listeria monocytogenes, is a major foodborne pathogen, and its control is becoming difficult because of widespread emergence of drug resistance strains. Chorismate synthase (CS), an essential enzyme of shikimate pathway present only in bacteria, fungi, plant and some apicomplexan parasites, is a validated potential antimicrobial drug target. Antimicrobial development through the elucidation of essential structural features of the CS of L. monocytogenes (LmCS), identification and prioritization of potential lead compounds targeted against LmCS were done. Structure-based virtual screening and docking studies were performed using Autodock tools to retrieve potential candidates with high affinity binding against LmCS model from several ligand repositories. The potency of binding was also checked with other structurally similar CS from Streptococcus pneumoniae (SpCS) and Mycobacterium tuberculosis (MtCS). The sequence and structural studies revealed LmCS was similar to be other CS structures (1Q1L, 1QXO, 1R52, 1R53, 1SQ1, 1UM0, 1UMF, 1ZTB, 2011, 2012, 4ECD and 2G85) with each monomer presenting β-α-β sandwich topology with a central helical core. Molecular docking studies and ADME/Tox results revealed that ZINC03803450 and ZINC20149031 were most potent molecules binding into the active site of LmCS. Other two ligands ZINC13387711 and ZINC16052528 showed a strong binding affinity score against all three structures (LmCS, SpCS and MtCS) and bind to LmCS with the predicted inhibition constant (Ki) values of 22.94 nM and 35.84 nM, respectively. A reported benzofuran-3[2H]-one analog CHEMBL135212 with good ADME/Tox properties and experimental IC50 (nM) value of 7000 nM with SpCS could also be considered as a potential inhibitor of LmCS, as compared to previously reported 41 benzofuran-3[2H]-one analogs against SpCS. This information will assist in discovering those compounds that may act as potent CS inhibitors. Further experimental studies and evaluation of structure-activity relationship could help in the development of potential inhibitors against listeriosis, as well as antibacterial chemotherapy.

Fish antifreeze proteins: Computational analysis and physicochemical characterization.

Antifreeze proteins (AFPs) protect organisms from freezing and shows great diversity in structure, and they have been found in a variety of organisms. In this study, a total of 15 antifreeze proteins of fish were selected where they represent distinct physicochemical and structural features. The present paper uses bioinformatics approach to describe the physiochemical, functional and structural properties of Antifreeze proteins. Several Physico-chemical properties such as pI, EC, AI, GRAVY and instability index are computed and provide data about these proteins and their properties. The result of primary structure analysis infers that, fish antifreeze proteins are mostly hydrophobic. Disulfide bridges and secondary structures were analyzed using CYS_REC and SOPMA respectively. The three dimensional structure of Antifreeze proteins is predicted by using three homology modeling server Geno3D, Swiss-model and CPHmodels. The model was evaluated with PROCHECK, WHAT IF, and ProSA programs. Model visualization and analysis was done with Pymol. These structures will provide a good foundation for functional analysis of experimentally derived crystal structures.