Activity-based protein profiling: an efficient approach to study serine hydrolases and their inhibitors in mammals and microbes

Chen, Biao; Ge, Sha-Sha; Zhao, Yuting; Chen, Chong; Yang, Song

doi:10.1039/c6ra20006k

Cited by 10 publications

(15 citation statements)

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“…Fluorophosphonates (FPs) are a class of electrophilic phosphonates that target serine hydrolases (SHs), and have been investigated by Yang and co‐workers . The use of FPs can be traced back to the early 1950s when diisopropyl fluorophosphate ( 9 ; Figure ) was first used for the inhibition of SH .…”

Section: Applications In Activity‐based Protein Profiling (Abpp)mentioning

confidence: 99%

The Application of Fluorine‐Containing Reagents in Structural Proteomics

2020

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Structural proteomics refers to large‐scale mapping of protein structures in order to understand the relationship between protein sequence, structure, and function. Chemical labeling, in combination with mass‐spectrometry (MS) analysis, have emerged as powerful tools to enable a broad range of biological applications in structural proteomics. The key to success is a biocompatible reagent that modifies a protein without affecting its high‐order structure. Fluorine, well‐known to exert profound effects on the physical and chemical properties of reagents, should have an impact on structural proteomics. In this Minireview, we describe several fluorine‐containing reagents that can be applied in structural proteomics. We organize their applications around four MS‐based techniques: a) affinity labeling, b) activity‐based protein profiling (ABPP), c) protein footprinting, and d) protein cross‐linking. Our aim is to provide an overview of the research, development, and application of fluorine‐containing reagents in protein structural studies.

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Section: Applications In Activity‐based Protein Profiling (Abpp)mentioning

confidence: 99%

The Application of Fluorine‐Containing Reagents in Structural Proteomics

2020

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“…Fluorphosphonate (FPs) sind eine Klasse elektrophiler Phosphonate, die Serinhydrolasen (SHs) adressieren und die von Yang und Mitarbeitern untersucht wurden . Die Verwendung von FPs kann bis in die frühen 1950er zurückverfolgt werden, als Diisopropylfluorphosphonat ( 9 ; Abbildung ) zum ersten Mal für die SH‐Inhibition verwendet wurde .…”

Section: Anwendung Im Aktivitäts‐basierten Protein‐profiling (Abpp)unclassified

Fluorierte Reagenzien in der Strukturproteomik

2020

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Das Gebiet der Strukturproteomik befasst sich mit der umfassenden Kartierung von Proteinstrukturen, mit dem Ziel, die Beziehung zwischen Proteinsequenz, ‐struktur und ‐funktion zu verstehen. Die Kombination aus chemischer Markierung und Massenspektrometrie‐Analytik hat sich zu einem beliebten Ansatz für biologische Fragestellungen in der Strukturproteomik entwickelt. Hierbei sind biokompatible Reagenzien, die Proteine modifizieren, ohne deren höhere Ordnung zu beeinflussen, der Schlüssel zum Erfolg. Fluor ist bestens dafür bekannt, die physikochemischen Eigenschaften von Reagenzien zu verändern, und spielt daher in der Strukturproteomik eine immer bedeutendere Rolle. In diesem Kurzaufsatz beschreiben wir die Verwendung fluorierter Reagenzien im Bereich der Strukturproteomik. Dabei beziehen wir uns auf MS‐basierte Techniken: a) Affinitätsmarkierung b) Aktivitäts‐basiertes Protein‐Profiling (ABPP), c) Protein‐Footprinting sowie d) Protein‐Crosslinking. Unser Ziel ist es, den Stand der Forschung sowie die Entwicklungen und Anwendungen von fluorierten Reagenzien in der Proteinstrukturanalytik zusammenzufassen.

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“…Activity-based protein profiling (ABPP) has emerged as a powerful and versatile chemical proteomic platform for characterizing the function of enzymes and for rapidly identifying novel targets (Chen et al, 2016;Cravatt et al, 2008;Spradlin et al, 2019;Wright and Sieber, 2016). Central to ABPP is the use of activity-based probes (ABPs), which covalently modify the active sites of enzymes.…”

Section: Introductionmentioning

confidence: 99%

The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites

Yoo

Schulze

Stokes

et al. 2020

Cell Chemical Biology

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Salinipostin A (Sal A) is a potent antimalarial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α /β serine hydrolase domains, and several are essential for parasite growth. One of the essential targets displays high homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate. This Sal A target is inhibited by the anti-obesity drug Orlistat, which disrupts lipid metabolism and produces disorganized and stalled schizonts similar to Sal A. Resistance selections yielded parasites that showed only minor reductions in sensitivity and that acquired mutations in a protein linked to drug resistance in Toxoplasma gondii. This inability to evolve efficient resistance mechanisms combined with the non-essentiality of human homologs makes the serine hydrolases identified here promising antimalarial targets..

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Activity-based protein profiling: an efficient approach to study serine hydrolases and their inhibitors in mammals and microbes

Abstract: This review focuses on the identification of serine hydrolases and their inhibitors in mammals and microbes with activity-based protein profiling (ABPP).

Cited by 10 publications

References 154 publications

The Application of Fluorine‐Containing Reagents in Structural Proteomics

The Application of Fluorine‐Containing Reagents in Structural Proteomics

Fluorierte Reagenzien in der Strukturproteomik

The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites

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