Bile-Salt-Protein Interactions

Nair, Padmanabhan P.

doi:10.1007/978-1-4615-7563-4_3

Cited by 4 publications

(3 citation statements)

References 85 publications

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“…Bile salts, integral for dietary fat digestion and absorption in the small intestine (Chiang & Ferrell, 2018 ), have diverse roles, including the regulation of cellular homeostasis and the modulation of gut bacterial growth (Larabi et al, 2023 ). Moreover, bile salts can alter protein structure and function, and are known to induce a compact conformation of TcdB (Aguirre et al, 2021 ; Cremers et al, 2014 ; Nair, 1976 ; Tam et al, 2020 ; Winston & Theriot, 2016 ; Zhuang et al, 2017 ). However, the impact of bile on the binding and inhibitory capacity of V H Hs towards TcdB remains relatively unexplored.…”

Section: Discussionmentioning

confidence: 99%

Fit‐for‐purpose heterodivalent single‐domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile

Rodriguez Rodriguez,

Nordvang,

Petersson

et al. 2024

Protein Science

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Single‐domain antibodies (sdAbs), such as VHHs, are increasingly being developed for gastrointestinal (GI) applications against pathogens to strengthen gut health. However, what constitutes a suitable developability profile for applying these proteins in a gastrointestinal setting remains poorly explored. Here, we describe an in vitro methodology for the identification of sdAb derivatives, more specifically divalent VHH constructs, that display extraordinary developability properties for oral delivery and functionality in the GI environment. We showcase this by developing a heterodivalent VHH construct that cross‐inhibits the toxic activity of the glycosyltransferase domains (GTDs) from three different toxinotypes of cytotoxin B (TcdB) from lineages of Clostridium difficile. We show that the VHH construct possesses high stability and binding activity under gastric conditions, in the presence of bile salts, and at high temperatures. We suggest that the incorporation of early developability assessment could significantly aid in the efficient discovery of VHHs and related constructs fit for oral delivery and GI applications.

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Section: Discussionmentioning

confidence: 99%

Fit‐for‐purpose heterodivalent single‐domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile

Rodriguez Rodriguez,

Nordvang,

Petersson

et al. 2024

Protein Science

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“…The detergent-property of bile salts [9] and the capacity of ionic detergents to split off the enzyme-bound pyridoxal phosphate [37,38] are well known. In order to examine whether sodium cholate had any effect on the coenzyme absorption spectrum of phosphorylase h, the enzyme (10 mg/ml, in 1 mM EDTA, 20 mM glycerol-2-P buffer, pH 6.8) was treated with 5, 10, and 20mM sodium cholate.…”

Section: Effkct Qf' Sodium Cholutr On [He Structure Of' Phosphorylase Bmentioning

confidence: 99%

“…In an effort to investigate the problem of 'hydrophobic activation of phosphorylase h', we have examined the catalytic and structural behaviour of phosphorylase molecule in presence of bile salts. These steroid molecules form a unique group of biological detergents, are amphiphilic in nature possessing distinct lipophilic and hydrophilic centers and they are able to modulate the biological activity of various enzymes through specific ligand-protein interactions [9]. We have found that sodium cholate was able to partially activate phosphorylase h in absence of AMP and that this activation was highly specific.…”

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confidence: 99%

Effect of Sodium Cholate on the Catalytic and Structural Properties of Phosphorylase b

et al. 1983

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Sodium cholate at millimolar concentration is able to induce activity in rabbit muscle phosphorylase b in the absence of AMP. The maximum activation of the enzyme in presence of 7 mM sodium cholate was 24 of that achieved by 1 mM AMP. Other bile salts tested showed a negligible activating effect. The K, for AMP was lowered fivefold by 5 m M of the steroid detergent, while the cooperative binding of the nucleotide was abolished Phosphorylase h', a modified form of phosphorylase in which the phosphorylation site has been removed by limited tryptic attack, presented an activation profile similar to that of phosphorylase b. In contrast, phosphorylase u was inhibited by the bile salt, while the activity of liver phosphorylase b was not significantly affected. Modification of the AMP site of the enzyme with 2,3-butanedione could not inhibit sodium-cholate-induced activity. tert-Butanol, an organic solvent activator of phosphorylase h, was found to enhance the activity induced by sodium cholate. The interaction of sodium cholate and phosphorylase h was also followed by difference spectroscopy using a fluorescein isothiocyanate -phosphorylase b conjugate. Furthermore, measurements of electron spin resonance demonstrated that the mobility of a spin-label bound at buried -NH, groups of phosphorylase h decreases cooperatively with increasing bile salt concentration.

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Probing of bile salt aggregation using fluorogenic dansylated-gemcitabine marker

Jaiswal,

Gadly,

Chakraborty

et al. 2024

Optics & Laser Technology

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Bile-Salt-Protein Interactions

Cited by 4 publications

References 85 publications

Fit‐for‐purpose heterodivalent single‐domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile

Fit‐for‐purpose heterodivalent single‐domain antibody for gastrointestinal targeting of toxin B from Clostridium difficile

Effect of Sodium Cholate on the Catalytic and Structural Properties of Phosphorylase b

Probing of bile salt aggregation using fluorogenic dansylated-gemcitabine marker

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