Activity‐Based Protein Profiling (ABPP) of Oxidoreductases

Abstract

Over the last two decades, activity‐based protein profiling (ABPP) has been established as a tremendously useful proteomic tool for measuring the activity of proteins in their cellular context, annotating the function of uncharacterized proteins, and investigating the target profile of small‐molecule inhibitors. Unlike hydrolases and other enzyme classes, which exhibit a characteristic nucleophilic residue, oxidoreductases have received much less attention in ABPP. In this minireview, the state of the art of ABPP of oxidoreductases is described and the scope and limitations of the existing approaches are discussed. It is noted that several ABPP probes have been described for various oxidases, but none so far for a reductase, which gives rise to opportunities for future research.

Proteomic Approaches to Study SARS-CoV-2 Biology and COVID-19 Pathology

“…A number of enzymatic activities can be targeted, including cysteine proteases, cathepsins, kinases, metalloproteases, serine proteases, and oxidoreductases. 179 , 180 , 183 …”

Chemistry for the Identification of Therapeutic Targets: Recent Advances and Future Directions

“…Accordingly, the development of specific ABPs for oxidoreductases require a careful study of the chemical transformation being carried out by the enzyme. [25] Among the most representative examples are the alkynyl-containing ABPs against P450 monoxygenases where one terminal alkyne is used as the bioorthogonal group to conjugate the desired reporter by click chemistry and the other terminal alkyne acts as the warhead, being converted into a highly electrophilic ketene by the P450 oxidase ( Figure 5A). [26] Similar strategies have enabled the development of ABPs against flavin-dependent monoamineoxidase (MAO) ( Figure 5B), [27] myeloperoxidase [28] (Figure 5C) or aldehyde dehydrogenases ( Figure 5D).…”

“…This feature adds an additional difficulty to annotate their function on a gene sequence level, as the encoded amino acids are not characteristic for their catalytic function. Accordingly, the development of specific ABPs for oxidoreductases require a careful study of the chemical transformation being carried out by the enzyme [25] . Among the most representative examples are the alkynyl‐containing ABPs against P450 monoxygenases where one terminal alkyne is used as the bioorthogonal group to conjugate the desired reporter by click chemistry and the other terminal alkyne acts as the warhead, being converted into a highly electrophilic ketene by the P450 oxidase (Figure 5A) [26] .…”

Capture and Identification of Dual Specificity Mitogen-Activated Protein Kinase Kinase 7 as a Direct Proteomic Target of Berberine to Affect the c-JunN-Terminal Kinase Pathway

“…Furthermore, several direct proteomic targets of BBR, such as NEK7, UHRF1, RXRα, actin and ephrin-B2, 18,24,25,28,29 have been identified to explain its synergistic effects. 24,30,31 The JNK pathway is mainly activated by various damage associated molecular patterns (DAMPs) including proinflammatory cytokines (tumor necrosis factor (TNF)-α and IL-1α), and the stimulation of JNK pathway gives rise to a marked increase of JNK phosphorylation (p-JNK) level, which lead to the progression of inflammatory, neurodegenerative and cell proliferative related diseases. 12,15,25,26 It is worth noting that BBR could suppress p-JNK to alleviate inflammation-related symptoms, such as obesity, insulin resistance, and exert effects on tumorous and neurodegenerative diseases.…”