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The multifaceted nature of peroxiredoxins in chemical biology
Curr Opin Chem Biol. 2023 Jun 27;76:102355. doi: 10.1016/j.cbpa.2023.102355. Online ahead of print.ABSTRACTPeroxiredoxins (Prx), thiol-dependent peroxidases, were first identified as H2O2 detoxifiers, and more recently as H2O2 sensors, intermediates in redox-signaling pathways, metabolism modulators, and chaperones. The multifaceted nature of Prx is not only dependent on their peroxidase activity but also strongly associated with specific protein-protein interactions that are being identified, and where the Prx oligomerization dynamics plays a role. Their oxidation by a peroxide substrate forms a sulfenic acid that opens a...
Source: Current Opinion in Chemical Biology - June 29, 2023 Category: Biochemistry Authors: Sebasti án F Villar Gerardo Ferrer-Sueta Ana Denicola Source Type: research

Recent advances in developing degraders & amp; inhibitors of lysine methyltransferases
Curr Opin Chem Biol. 2023 Jun 26;76:102356. doi: 10.1016/j.cbpa.2023.102356. Online ahead of print.ABSTRACTOver the last several decades, there has been continued interest in developing novel therapeutic approaches targeting protein lysine methyltransferases (PKMTs). Along with PKMT inhibitors, targeted protein degradation (TPD) has emerged as a promising strategy to attenuate aberrant PKMT activity. Particularly, proteolysis targeting chimeras (PROTACs) effectively eliminate PKMTs of interest, suppressing all enzymatic and non-enzymatic functions. PROTACs and other TPD approaches add new depth to PKMT research and novel t...
Source: Current Opinion in Chemical Biology - June 28, 2023 Category: Biochemistry Authors: Julia Velez H Ümit Kaniskan Jian Jin Source Type: research

Small molecule fluorescent probes for the study of protein phase separation
Curr Opin Chem Biol. 2023 Jun 24;76:102354. doi: 10.1016/j.cbpa.2023.102354. Online ahead of print.ABSTRACTLiquid-liquid phase separation (LLPS) and liquid-solid phase transitions (LSPT) play crucial roles in biological systems, including sorting biomolecules, facilitate the transport of substrates for assembly, and accelerate the formation of metabolic and signaling complexes. Efforts towards improved characterization and quantification of phase separated species remain of outstanding interest and priority. In this review, we cover recent advances and the strategies used with small molecule fluorescent probes for the stud...
Source: Current Opinion in Chemical Biology - June 26, 2023 Category: Biochemistry Authors: Tze Cin Owyong Jiamin Zhao Yuning Hong Source Type: research

Emergence of (hydro)persulfides as suppressors of lipid peroxidation and ferroptotic cell death
Curr Opin Chem Biol. 2023 Jun 23;76:102353. doi: 10.1016/j.cbpa.2023.102353. Online ahead of print.ABSTRACTRecognition of the prevalence of hydropersulfides (RSSH) and characterization of their enhanced two-electron reactivity relative to thiols have led to their implication in maintaining cellular redox homeostasis, in addition to other potential roles. Recent attention on the one-electron reactivity of RSSH has uncovered their potent radical-trapping antioxidant activity, which enables them to inhibit phospholipid peroxidation and associated cell death by ferroptosis. Herein, we briefly review key aspects of the reactivi...
Source: Current Opinion in Chemical Biology - June 25, 2023 Category: Biochemistry Authors: Zijun Wu Uladzimir Barayeu Danny Schilling Tobias P Dick Derek A Pratt Source Type: research

Chemical biology approaches to uncovering nuclear ROS control
Curr Opin Chem Biol. 2023 Jun 21;76:102352. doi: 10.1016/j.cbpa.2023.102352. Online ahead of print.ABSTRACTHeightened concentrations of reactive metabolites, including reactive oxygen species (ROS), can damage all macromolecules leading to the erosion of cellular fidelity. In this regard, the control of ROS in the nuclues is essential for cellular homeostasis, and dysregulation of nuclear ROS has been attributed to multiple pathologies and the mechanism of action of certain chemotherapies. How nuclear ROS is generated, detoxified and sensed is poorly understood, and stems in part, from a historical lack of tools that allow...
Source: Current Opinion in Chemical Biology - June 23, 2023 Category: Biochemistry Authors: Junbing Zhang Liron Bar-Peled Source Type: research

Cysteine and methionine oxidation in thrombotic disorders
Curr Opin Chem Biol. 2023 Jun 16;76:102350. doi: 10.1016/j.cbpa.2023.102350. Online ahead of print.ABSTRACTThrombosis is the leading cause of death in many diseased conditions. Oxidative stress is characteristic of these conditions. Yet, the mechanisms through which oxidants become prothrombotic are unclear. Recent evidence suggests protein cysteine and methionine oxidation as prothrombotic regulators. These oxidative post-translational modifications occur on proteins that participate in the thrombotic process, including Src family kinases, protein disulfide isomerase, β2 glycoprotein I, von Willebrand factor, and fibrino...
Source: Current Opinion in Chemical Biology - June 18, 2023 Category: Biochemistry Authors: Moua Yang Brian C Smith Source Type: research