Mycosporine-Like Amino Acids as a Potential Inhibitor of Tyrosinase-Related Protein 1: Computational Screening, Pharmacokinetics, and Molecular Dynamics Simulation.

Melanin is the major pigment responsible for the coloring of mammalian skin, hair, and eyes to defend against ultraviolet radiation. However, excessive melanin production has resulted in numerous types of hyperpigmentation disorders. Tyrosinase-related protein 1 (TYRP1) is a transmembrane glycoprotein enzyme found in many organisms, including humans, that plays an important role in melanogenesis. Thus, controlling the enzyme activity of TYRP1 with tyrosinase inhibitors is a vital step in the treatment of hyperpigmentation problems in humans. In the present investigation, virtual screening, pharmacokinetics, drug docking, and molecular dynamics (MD) simulation were used to find the most potent drug as an inhibitor of TYRP1 to effectively treat hyperpigmentation disorder. The 3D structure of TYRP1 was retrieved from the Protein Data Bank (PDB) database (PDB ID: 5M8M) and validated by the Ramachandran plot. Pharmacokinetics and drug-likeness showed that mycosporine 2 glycine (M2G) and shinorine (SHI) were the best compounds over other ligands in the same (P-1) structural pose. However, MD simulations of the M2G showed the highest CDOCKER interaction energy (-45.182 kcal/mol) and binding affinity (-65.0529 kcal/mol) as compared to SHI and reference drugs. The molecular binding modes RMSD and RMSF plots have exhibited more relevance to the M2G ligand in comparison to other drug ligands. The bioactivity and ligand efficiency profiles revealed that M2G is the most effective compound as a TYRP1 inhibitor. Thus, M2G could be used as a most effective drug for developing valuable sunscreen products to cure hyperpigmentation-related diseases.

Effects of ultraviolet and photosynthetically active radiation on morphogenesis, antioxidants and photoprotective defense mechanism in a hot-spring cyanobacterium Nostoc sp. strain VKB02.

The continuous increase in global temperature and ultraviolet radiation (UVR) causes profound impacts on the growth and physiology of photosynthetic microorganisms. The hot-spring cyanobacteria have a wide range of mitigation mechanisms to cope up against current unsustainable environmental conditions. In the present investigation, we have explored the indispensable mitigation strategies of an isolated hot-spring cyanobacterium Nostoc sp. strain VKB02 under simulated ultraviolet (UV-A, UV-B) and photosynthetically active radiation (PAR). The adaptive morphological changes were more significantly observed under PAB (PAR, UV-A, and UV-B) exposure as compared to P and PA (PAR and UV-A) irradiations. PAB exposure also exhibited a marked decline in pigment composition and photosynthetic efficiency by multi-fold increment of free radicals. To counteract the oxidative stress, enzymatic and non-enzymatic antioxidants defense were significantly enhanced many folds under PAB exposure as compared to the control. In addition, the cyanobacterium has also produced shinorine as a strong free radicals scavenger and excellent UV absorber for effective photoprotection against UV radiation. Therefore, the hot-spring cyanobacterium Nostoc sp. strain VKB02 has unique defense strategies for survival under prolonged lethal UVR conditions. This study will help in the understanding of environment-induced defense strategies and production of highly value-added green photo-protectants for commercial applications.