Structural and mechanistic insights into oxidative biaryl coupling to form the arylomycin core by an engineered CYP450.

Arylomycin, a potent antibiotic targeting bacterial signal peptidase, is difficult to synthesize experimentally due to its poor to moderate yields and the formation of a mixture of compounds. A recent experimental bioengineering work shows that the core of arylomycin can be efficiently synthesized by engineering the cytochrome P450 enzyme from sp.; however, the mechanism of the same was not elucidated.

Tyr 118-Mediated Electron Transfer is Key to the Chlorite Decomposition in Heme-Dependent Chlorite Dismutase.

Chlorite dismutase (Cld) is a crucial enzyme that catalyzes the decomposition of chlorite ions into chloride ions (Cl) and molecular oxygen (O). Despite playing an important role in the detoxification of toxic chlorite ions, the mechanism of cleavage of the Cl-O bond by Cld remains highly debatable. The present study highlights the mechanism of such Cl-O bond cleavage in Cld using sophisticated computational tools such as hybrid quantum mechanical/molecular mechanical calculations and long-time scale molecular dynamics simulations.

Identification of a novel inhibitor of SARS-CoV-2 main protease: an in silico, biochemical, and cell-based approach.

The recurrent nature of coronavirus outbreaks, severity of the COVID-19 pandemic, rapid emergence of novel variants, and concerns over the effectiveness of existing vaccines against novel variants have highlighted the need to develop therapeutic interventions. Targeted efforts to identify inhibitors of crucial viral proteins are the preferred strategy. In this study, we screened FDA-approved and natural product libraries using in silico approach for potential hits against the SARS-CoV-2 main protease (Mpro) and experimentally validated their potency using in vitro biochemical and cell-based assays.

Esterase Specific Fluorescent Probe: Mechanistic Understanding Using QM/MM Calculation and Cell States Discrimination.

Esterases enzymes regulate the body's homeostasis by catalyzing the hydrolysis of various esters. These are also involved in protein metabolism, detoxification, and signal transmission. Most importantly, esterase plays a significant role in cell viability and cytotoxicity assays.

Computations reveal a crucial role of an aromatic dyad in the catalytic function of plant cytochrome P450 mint superfamily.

Enzymes are highly specific for their native functions, however with advances in bioengineering tools such as directed evolution, several enzymes are being repurposed for the secondary function of contemporary significance(Khersonsky and Tawfik, 2010 [1]. Due to the functional versatility, the Cytochrome P450 (CYP450) superfamily has become the ideal scaffold for such bioengineering. In the current study, using MD (molecular dynamics) simulations and hybrid QM/MM (Quantum mechanics/molecular mechanics) calculations, we have studied the mechanism of spontaneous emergence of a secondary function due to a single site mutation in two plant CYP450 enzymes from the mint family.

The Performance of Different Water Models on the Structure and Function of Cytochrome P450 Enzymes.

Modeling approaches and modern simulations to investigate the biomolecular structure and function rely on various methods. Since water molecules play a crucial role in all sorts of chemistry, the accurate modeling of water molecules is vital for such simulations. In cytochrome P450 (CYP450), in particular, water molecules play a key role in forming active oxidant that ultimately performs oxidation and metabolism.

Deciphering the immunogenic T-cell epitopes from spike protein of SARS-CoV-2 concerning the diverse population of India.

Scientists are rigorously looking for an efficient vaccine against the current pandemic due to the SARS-CoV-2 virus. The reverse vaccinology approach may provide us with significant therapeutic leads in this direction and further determination of T-cell/B-cell response to antigen. In the present study, we conducted a population coverage analysis referring to the diverse Indian population.