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The 1, 25-dihydroxyvitamin D3 24-hydroxylase, is an enzyme that in humans is encoded by the CYP24A1gene. The P450s are considered to have a central role in chemical carcinogenesis and are involved in tumor initiation and promotion as they can activate or deactivate many carcinogens. Furthermore, the P450s can influence the response of established tumors to anti-cancer drugs as P450s are involved in the metabolism of several anti-cancer drugs. CYP24A1 protein, member of Cytochrome P450 family which contains more than 50 enzymes, is found expressed in kidney and also in other tissues both healthy and cancerous. The CYP24A1 protein exists in two states-open state and closed state both of which will be studied in this research. Both open and closed state of CYP24A1 were first modeled and further docked with VID-400, an imidazole derivative seen to be a specific inhibitor of CYP24A1, and also with the inhibitors obtained after ligand based searching using VID-400 as the query in the PubChem database. The docking interactions for the inhibitors which gave positive results were further validated using Molecular dynamics simulation. The transition from open to closed form was also analyzed by comparing results of MD simulation of the ligand-free form and ligand-bound form of CYP24A1 and its transition to a closed binding pocket after the binding of the inhibitor.

Background: The wastewater disposal into the water bodies without removing the toxic heavy metals and other industrial impurities is a major issue these days. These heavy metals cause serious health issues to the human and animal life and also harm the environment and reduce the productivity of crops. A potent microorganism resistant to hexavalent chromium was isolated. The activity of this isolated strain was analyzed using in silico studies. Methods: In this study, a chromium-resistant fungus was isolated from the soil of the dumping sites of the tanneries in Kanpur, UP, India, followed by isolation by serial dilution, plating method, and finally, genome sequencing. It was identified as Aspergillus proliferans LA that is submitted to the National Collection for Industrial Microorganisms (NCIM) database with accession no. NCIM-1473. In the current study, the comparative analysis of the protein sequence of A. proliferans (NCIM-1473) was done against the known 53 protein sequences of the fungus and bacterial strains already reported for their chromium-resistant nature. The physical and chemical parameters of the known and isolated chromium-resistant proteins were analyzed using the ProtParam tool. The comparative study on the sequence and structural alignment of known and isolated chromium-resistant protein was done using EMBOSS-NEEDLE and FATCAT, respectively. Results: In this analysis, the top 10 strains showing similarity with A. proliferans (NCIM-1473) were reported and among which ChrI, chromium regulatory protein Cupriavidus metallidurans CH34 was showing maximum similarity with isolated chromium resistant protein for all the analysis, namely ProtParam, sequence, and FATCAT analysis. This strain, Cupriavidus metallidurans CH34, has been reported resistant against eight heavy metals, one of which is chromate, and was first identified in the heavy-metal contaminated sludge in a settling tank of Belgium. Conclusion: These studies conclude that the strain isolated in our laboratory (accession no. NCIM-1473) is potentially chromium resistant and a unique strain.

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Heavy metal salts are widely used in the tanning process in the form of Chrome alum and Chromium[III] sulfate. It is a highly toxic metal and cannot be degraded thus deposited and incorporated in water, sediment and aquatic ecosystems which poses various respiratory, skin and other health issues to humans and also cause serious issues to microbial, plant and aquatic life. The cost of these heavy metal salts is high due to which the tanners need a lot of investment for the tanning process because of its abundant use. So, to overcome such issues numerous techniques have been developed for the recovery and reuse of these heavy metal salts from the wastewater of the tanneries to reduce the pollution in the wastewater streams and exempt the tanners from the high cost of these salts.