The Mycobacterium tuberculosis H37Rv genome encodes 20 cytochromes P450, including P450s crucial to infection and bacterial viability. Many M. tuberculosis P450s remain uncharacterized, suggesting that their further analysis may provide new insights into M. tuberculosis metabolic processes and new targets for drug discovery. CYP126A1 is representative of a P450 family widely distributed in mycobacteria and other bacteria. Here we explore the biochemical and structural properties of CYP126A1, including its interactions with new chemical ligands. A survey of azole antifungal drugs showed that CYP126A1 is inhibited strongly by azoles containing an imidazole ring but not by those tested containing a triazole ring. To further explore the molecular preferences of CYP126A1 and search for probes of enzyme function, we conducted a high throughput screen. Compounds containing three or more ring structures dominated the screening hits, including nitroaromatic compounds that induce substrate-like shifts in the heme spectrum of CYP126A1. Spectroelectrochemical measurements revealed a 155-mV increase in heme iron potential when bound to one of the newly identified nitroaromatic drugs. CYP126A1 dimers were observed in crystal structures of ligand-free CYP126A1 and for CYP126A1 bound to compounds discovered in the screen. However, ketoconazole binds in an orientation that disrupts the BC-loop regions at the P450 dimer interface and results in a CYP126A1 monomeric crystal form. Structural data also reveal that nitroaromatic ligands “moonlight” as substrates by displacing the CYP126A1 distal water but inhibit enzyme activity. The relatively polar active site of CYP126A1 distinguishes it from its most closely related sterol-binding P450s in M. tuberculosis, suggesting that further investigations will reveal its diverse substrate selectivity.
Objective: This study aims in constructing a three-dimensional modeled Spike glycoprotein structure of novel variants of SARS CoV-2. Methods: The protein models were constructed using SWISS-Model online tool. The constructed protein models were submitted in online database called Protein Model Database (PMDB) for public access to the structures. Results: A total of 70 protein sequences of Spike glycoprotein of novel variants of SARS CoV-2 were retrieved from NCBI virus database and were subjected for sequence similarity search and homology model construction. The constructed models were subjected for Ramachandran plot analysis to validate the quality of the structures. A total of 40 structures were considered to be of significant quality and were submitted to the online database PMDB. Conclusion: These predicted structures would help greatly in identification and drug design. This would greatly help in drug development and personalized drug treatment against different variants of the pathogen. This database would significantly support the structure-based computational drug design applications toward personalized medicine against the variants of concern of SARS CoV-2.
“Actinobacteria” are of significant economic value to mankind since agriculture and forestry depend on their soil system contribution. The organic stuff of deceased creatures is broken down into soil, and plants are able to take the molecule up again. Actinobacteria can be used for sustainable agriculture as biofertilizers for the improvement of plant growth or soil health by promoting different plant growth attributes, such as phosphorus and potassium solubilization, production of iron-chelating compounds, phytohormones, and biological nitrogen attachment even under the circumstances of natural and abiotic stress. Nanotechnology has received considerable interest in recent years due to its predicted impacts on several key fields such as health, energy, electronics, and the space industries. Actinobacterial biosynthesis of nanoparticles is a dependable, environmentally benign, and significant element toward green chemistry, which links together microbial biotechnology and nanobiology. Actinobacterial-produced antibiotics are common in nearly all of the medical treatments, and they are also recognized to aid in the biosynthesis of excellent surface and size properties of nanoparticles. Bioremediation using microorganisms is relatively safe and more efficient. Actinobacteria use carbon toxins to synthesize economically viable antibiotics, enzymes, and proteins as well. These bacteria are the leading microbial phyla that are beneficial for deterioration and transformation of organic and metal substrates.
As the study on utilization of solar energy is still ongoing, its utility in day- to-day life despite of being easy isn’t wide spread. Hence, it becomes important to set up small systems and analyze the overall impact and then slowly shift the electrical system from the conventional form to this eco-friendly solution. This project is an endeavor of understanding the pointers and designing solar based electrical circuit which is capable of running daily appliances along with studying the effect of variation of circuit design on the load. Analyzing the electrical parameters of the solar cells and thus setting up a circuit with optimum productivity is focused. Furthermore, in this paper, the obstacles that hurdle the large scale implementation of solar energy system is discussed and possible solutions for the same are proposed.
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