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Variations of the Mycobacterium abscessus F-ATP synthase subunit a-c interface alter binding and potency of the anti-TB drug bedaquiline
The anti-tuberculosis therapeutic bedaquiline (BDQ) is used against Mycobacterium abscessus. In M. abscessus BDQ is only bacteriostatic and less potent compared to M. tuberculosis or M. smegmatis.
ReadATP binding by an F1Fo ATP synthase ε subunit is pH dependent, suggesting a diversity of ε subunit functional regulation in bacteria
F-type ATP synthases synthesize ATP, the universal energy source in most living cells. The enzyme consists of a membrane embedded Fo domain, which is composed of the membrane embedded proteolipid ring (c subunits), the collar-like a subunit which is asymmetrically wrapped around the c-ring, and the b subunit dimer which links the membrane embedded c-subunit ring and a subunit to the F1 domain.
ReadBinding properties of the anti-TB drugs bedaquiline and TBAJ-876 to a mycobacterial F-ATP synthase
Tuberculosis (TB), the deadly disease caused by *Mycobacterium tuberculosis* (*Mtb*), kills more people worldwide than any other bacterial infectious disease. There has been a recent resurgence of TB drug discovery activities, resulting in the identification of a number of novel [enzyme inhibitors](https://www.sciencedirect.com/topics/neuroscience/enzyme-inhibitor "Learn more about enzyme inhibitors from ScienceDirect's AI-generated Topic Pages").
ReadAn Alternative HIV-1 Non-Nucleoside Reverse Transcriptase Inhibition Mechanism: Targeting the p51 Subunit
The ongoing development of drug resistance in HIV continues to push for the need of alternative drug targets in inhibiting HIV. One such target is the Reverse transcriptase (RT) enzyme which is unique and critical in the viral life cycle—a rational target that is likely to have less off-target effects in humans.
ReadA second shell residue modulates a conserved ATP-binding site with radically different affinities for ATP
Prediction of ligand binding and design of new function in enzymes is a time-consuming and expensive process. Crystallography gives the impression that proteins adopt a fixed shape, yet enzymes are functionally dynamic. Molecular dynamics offers the possibility of probing protein movement while predicting ligand binding. Accordingly, we choose the bacterial F1Fo ATP synthase ε subunit to unravel why ATP affinity by ε subunits from Bacillus subtilis and Bacillus PS3 differs ~500-fold, despite sharing identical sequences at the ATP-binding site.
ReadCharacterizing the Hydration Properties of Proton Binding Sites in the ATP Synthase c-Rings of Bacillus Species.
The membrane-embedded domain of ATP synthases contains the c-ring, which translocates ions across the membrane, and its resultant rotation is coupled to ATP synthesis in the extramembranous domain. During rotation, the c-ring becomes accessible on both sides of the lipid bilayer to solvent via channels connected to the other membrane-embedded component, the a subunit, and thereby allows the ion to be released into the solvent environment.
ReadThe Molecular Basis for Purine Binding Selectivity in the Bacterial ATP Synthase ϵ Subunit
The ϵ subunit of ATP synthases has been proposed to regulate ATP hydrolysis in bacteria. Prevailing evidence supports the notion that when the ATP concentration falls below a certain threshold, the ϵ subunit changes its conformation from a non‐inhibitory down‐state to an extended up‐state that then inhibits enzymatic ATP hydrolysis by binding to the catalytic domain.
ReadExtending the Martini coarse-grained forcefield to N-glycans
Glycans play a vital role in a large number of cellular processes. Their complex and flexible nature hampers structure-function studies using experimental techniques. Molecular dynamics (MD) simulations can help in understanding dynamic aspects of glycans if the forcefield (FF) parameters used can reproduce key experimentally observed properties.
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