A scaffold protein that chaperones a cysteine-sulfenic acid in H2O2 signaling

International audienceIn $Saccharomyces\ cerevisiae$, Yap1 regulates an H$_2$O$_2$-inducible transcriptional response that controls cellular H$_2$O$_2$ homeostasis. H$_2$O$_2$ activates Yap1 by oxidation through the intermediary of the thiol peroxidase Orp1. Upon reacting with H$_2$O$_2$, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages into either an intermolecular disulfide with Yap1, leading to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. How the first of these two competing reactions, which is kinetically unfavorable, occurs was previously unknown. We show that the Yap1-binding protein Ybp1 brings together Orp1 and Yap1 into a ternary complex that selectively activates condensation of the Orp1 sulfenylated cysteine with one of the six Yap1 cysteines while inhibiting Orp1 intramolecular disulfide formation. We propose that Ybp1 operates as a scaffold protein and as a sulfenic acid chaperone to provide specificity in the transfer of oxidizing equivalents by a reactive sulfenic acid species

Phytotherapy in Inflammatory Lung Diseases: An Emerging Therapeutic Interventional Approach

Chronic obstructive pulmonary disease (COPD) and asthma are the most common inflammatory respiratory diseases related to an increase in mortality and morbidity. Generally, bronchodilators, ß- agonists, anticholinergics and theophylline used for treatment in these conditions and administered by inhalation for delivery, have localized and systematic effects. The adverse effects are due to pharmacodynamic and pharmacokinetic changes and especially drug-drug and drug-disease interactions. However, phytotherapy is classical and widespread throughout the world for the treatment of ailments. This chapter highlights cellular and molecular mediators involved in COPD and asthma, the shortcomings of current therapies and the emerging need of phytomedicines. Phytomedicine supports respiratory physiology, bronchial action and possesses antioxidants to maintain homeostasis