Mechanistic Insights into the Cofactor Binding Dynamics and Interaction between Telmisartan and Human Thiopurine S-Methyltransferase.

Thiopurine S-methyltransferase (TPMT) is crucial for catalyzing the inactivation and reducing the toxicity of thiopurine class of immunosuppressive drugs which are FDA-approved to treat autoimmune diseases and transplant rejection. Its complete or partial loss of activity during standard-dose thiopurine treatment causes severe bone marrow suppression and death. Therefore, FDA recommends testing TPMT activity to identify patients at high risk of developing life-threatening complications.

Development and Validation of Real-Time Allele-Specific PCR-Based Genotyping of the rs1042713 Variant in the ADRB2 Gene and Its Correlation with Salbutamol Response.

Asthma is a prevalent chronic respiratory disease influenced by genetic and environmental factors. The beta-2 adrenergic receptor (ADRB2) gene, located on chromosome 5q31-q32, plays a crucial role in bronchodilation by regulating airway smooth muscle relaxation through cyclic adenosine monophosphate (cAMP)-mediated signaling. Genetic variations in ADRB2, particularly + 46A > G (Arg16Gly, rs1042713) and + 79C > G (Gln27Glu, rs1042714), have been associated with altered receptor function, potentially impacting bronchodilator response to β2adrenergic receptor agonists such as salbutamol.

Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.

The social deficits following chronic stress conditions are linked to synaptic dysfunction in the brain. Complement system plays a critical role in synapse regulation. Although complement has been implicated in chronic stress-induced behavior deficits the cellular substrates and mechanisms underlying complement-mediated behavior changes under chronic stress conditions are not known.

Novel Insights Into the Dynamic Conformational Transitions and Active Site Plasticity of Human Immunoregulatory Cathepsin S.

Cathepsin S (CatS), a cysteine protease, catalyzes the cleavage of immunoregulatory peptides and mediates tissue destruction in autoimmune and inflammatory diseases. Plasticity of its ligand binding site and mechanisms of dynamic transitions between different conformational states are critical in drug discovery; however, knowledge of its entire conformational landscape and transition mechanisms remains incomplete. Therefore, we investigated the atomic-level interactions between active site cleft residues that contribute to its structural and functional plasticity.