Tracking nitroxyl-derived posttranslational modifications of phospholamban in cardiac myocytes

Mundiña‐Weilenmann, Cecilia; Mattiazzi, Alicia

doi:10.1085/jgp.201912342

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2021

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“…The mechanism by which azanone affects the heart is a matter of intense research. It has been proposed that HNO donors enhance cardiac contractility, by targeting the regulatory protein phospholamban [ 74 , 75 ]. Keceli et al found that HNO reacts with Cys-41 and Cys-46 via the formation of the intramolecular disulfide bond, which forces conformational changes in the protein and enhances cardiac function as a result [ 74 ].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Azanone (HNO) Reactions with Thiols: Effect of pH

Smulik-Izydorczyk

Dębowska

Adamus

et al. 2021

Cell Biochem Biophys

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HNO (nitroxyl, IUPAC name azanone) is an electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present data on the pH-dependent kinetics of azanone reactions with the low molecular thiols glutathione and N-acetylcysteine, as well as with important serum proteins: bovine serum albumin and human serum albumin. The competition kinetics method used is based on two parallel HNO reactions: with RSH/RS− or with O2. The results provide evidence that the reaction of azanone with the anionic form of thiols (RS−) is favored over reactions with the protonated form (RSH). The data are supported with quantum mechanical calculations. A comprehensive discussion of the HNO reaction with thiolates is provided.

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Section: Introductionmentioning

confidence: 99%