Unveiling the versatility of the thioredoxin framework: Insights from the structural examination of DsbA1.

In bacteria the formation of disulphide bonds is facilitated by a family of enzymes known as the disulphide bond forming (Dsb) proteins, which, despite low sequence homology, belong to the thioredoxin (TRX) superfamily. Among these enzymes is the disulphide bond-forming protein A (DsbA); a periplasmic thiol oxidase responsible for catalysing the oxidative folding of numerous cell envelope and secreted proteins. Pathogenic bacteria often contain diverse Dsb proteins with distinct functionalities commonly associated with pathogenesis.

Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions.

Disulfide bond (Dsb) oxidoreductases involved in oxidative protein folding govern bacterial survival and virulence. Over the past decade, oligomerization has emerged as a potential factor that dictates oxidoreductase activities. To investigate the role of oligomerization, we studied three Dsb-like ScsC oxidoreductases involved in copper resistance: the monomeric StScsC, and the trimeric PmScsC and CcScsC.

Global analysis of endogenous protein disorder in cells.

Disorder and flexibility in protein structures are essential for biological function but can also contribute to diseases, such as neurodegenerative disorders. However, characterizing protein folding on a proteome-wide scale within biological matrices remains challenging. Here we present a method using a bifunctional chemical probe, named TME, to capture in situ, enrich and quantify endogenous protein disorder in cells.

Cardiorespiratory Fitness Benefits of High-Intensity Interval Training After Stroke: A Randomized Controlled Trial.

Background: Limited evidence supports the effects of short-interval high-intensity interval training (HIIT) for improving cardiorespiratory fitness (V̇Opeak) after stroke. We aimed to compare the effects of 12 weeks of short-interval HIIT versus moderate-intensity continuous training (MICT) on V̇Opeak, cardiovascular risk factors, and mobility outcomes among individuals ≥6 months poststroke.

Methods: This study was a multi-site, 12-week randomized controlled trial (NCT03614585) with an 8-week follow-up.

Fluoromethylketone-Fragment Conjugates Designed as Covalent Modifiers of EcDsbA are Atypical Substrates.

Disulfide bond protein A (DsbA) is an oxidoreductase enzyme that catalyzes the formation of disulfide bonds in Gram-negative bacteria. In Escherichia coli, DsbA (EcDsbA) is essential for bacterial virulence, thus inhibitors have the potential to act as antivirulence agents. A fragment-based screen was conducted against EcDsbA and herein we describe the development of a series of compounds based on a phenylthiophene hit identified from the screen.