Activity-Based Protein Profiling for the Study of Parasite Biology

Abstract

Parasites exist within most ecological niches, often transitioning through biologically and chemically complex host environments over the course of their parasitic life cycles. While the development of technologies for genetic engineering has revolutionised the field of functional genomics, parasites have historically been less amenable to such modification. In light of this, parasitologists have often been at the forefront of adopting new small-molecule technologies, repurposing drugs into biological tools and probes. Over the last decade, activity-based protein profiling (ABPP) has evolved into a powerful and versatile chemical proteomic platform for characterising the function of enzymes. Central to ABPP is the use of activity-based probes (ABPs), which covalently modify the active sites of enzyme classes ranging from serine hydrolases to glycosidases. The application of ABPP to cellular systems has contributed vastly to our knowledge on the fundamental biology of a diverse range of organisms and has facilitated the identification of potential drug targets in many pathogens. In this chapter, we provide a comprehensive review on the different forms of ABPP that have been successfully applied to parasite systems, and highlight key biological insights that have been enabled through their application.

Chalcones identify cTXNPx as a potential antileishmanial drug target

“…Whilst ABPP has been employed quite widely in cell biology, application to Leishmania spp. is limited [51][52][53][54][55][56][57]. Similarly, whilst many bioactive natural products have been adapted for use as ABPP agents to identify and validate new drug targets [58], despite being intrinsically electrophilic and therefore able to label a protein target, the use of chalcones in this context is surprisingly limited [32,59].…”

Eimeria proteins: order amidst disorder

“…Proteases, peptidases or proteinases are enzymes that catalyse hydrolysis of peptide bonds in all animal species. Proteases are classified based on their catalytic residues or mechanism as aspartyl, cysteine, serine, threonine and metalloproteases [ 117 ]. Proteases facilitate invasion of host cells, digestion of host proteins, host cell membrane degradation and evasion of host immune cells [ 117 ].…”

“…Proteases are classified based on their catalytic residues or mechanism as aspartyl, cysteine, serine, threonine and metalloproteases [ 117 ]. Proteases facilitate invasion of host cells, digestion of host proteins, host cell membrane degradation and evasion of host immune cells [ 117 ]. Proteases are also involved in developmental regulation of protozoan parasites, hydrolysis of proteins, nutrient uptake, and many members of cysteine proteases are major virulence factors of apicomplexans [ 118 ].…”

UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology

“…The frequent disconnect between protein expression and protein activity-for example, due to post-translational activation or inhibition-presents a significant challenge to cancer biologists aiming to link genotype to phenotype, as protein activity is not easily measured by standard proteomic approaches. An activitybased probe, or ABP, is a chemical tool, which can be applied to quantify the activity of a specific enzyme, or class of enzymes, in a physiologically relevant environment independently of protein expression [68][69][70][71][72]. ABPs also allow monitoring of specific target engagement by inhibitors or drugs (Fig.…”