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Low-molecular-weight (LMW) thiols play critical roles in maintaining redox buffer systems required for normal biological function. Glutathione (GSH) represents the most common LMW thiol found in Nature, but Gram-positive bacteria utilize bacillithiol (BSH) or mycothiol (MSH). Nitroxyl (HNO) can influence bacterial transcription through persulfide formation, a biological phenomenon that prompts the examination of the reactions of HNO with these LMW thiols. The development and application of colorimetric and enzymatic (Bacillus subtilis thioredoxin assay) methods combined with mass spectrometry of reaction products show the unique reactivity of BSH to favor sulfinamide adduct formation upon equimolar reaction with HNO. The reaction profile with GSH results in nearly equal distribution between sulfinamide:disulfide, whereas reaction with MSH only yields disulfide. These varied results led to the preparation of a group of BSH and MSH analogs, and their reactions with HNO reveal the requirement for a free amine group for sulfinamide formation. The thiol and amine group pKa's appear critical for sulfinamide generation, with the thiolate acting as a nucleophile to attack HNO and the ammonium donating a proton to facilitate water loss from the N-hydroxysulfenamide intermediate. Furthermore, the B. subtilis thioredoxin system efficiently reduces BSSB with a calculated KM_BSSB = 34 ± 3 μM and Vmax = 152 ± 3.4 nmol/min/nmol TrxR (kcat = 2.5 s−1), but does not reduce bacillithiol sulfinamide. Similarly, this thioredoxin reduces MSSM with a calculated KM_MSSM of 9 ± 2.1 μM and Vmax of 103 ± 7.1 nmol/min/nmol TrxR (kcat = 1.7 s−1). Bacillithiol possesses a unique structure that allows a rapid reaction with HNO to form a stable product that may provide a basis for antibiotic development or clues for further biological roles of nitroxyl.more » « lessFree, publicly-accessible full text available December 1, 2026
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Kang, Zhong-Bo; Samanta, Kajal; Shao, Ding Yu; Zeng, Yang-Li (, Journal of High Energy Physics)A<sc>bstract</sc> We apply the joint threshold and transverse momentum dependent (TMD) factorization theorem to introduce new threshold-TMD distribution functions, including threshold-TMD parton distribution functions (PDFs) and fragmentation functions (FFs). We apply Soft-Collinear Effective Theory and renormalization group methods to carry out QCD evolution for both threshold-TMD PDFs and FFs. We show the universality of threshold-TMD functions among three standard processes, i.e. the Drell-Yan production inppcollisions, semi-inclusive deep-inelastic scattering and back-to-back two hadron production ine+e−collisions. In the end, we present the numerical predictions for different threshold-TMD functions and also transverse momentum distributions atpp,ep, ande+e−collisions.more » « less
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