Papain-like cysteine proteases are the most numerous family of the cysteine protease class. They are expressed throughout the animal and plant kingdoms as well as in viruses and bacteria. More recently, this protease family has drawn attention as a potential pharmaceutical drug target in diseases characterized by excessive extracellular matrix degradation such as in osteoporosis, arthritis, vascular diseases, and cancer. Moreover, papain-like cysteine proteases have been identified as critical components of the life cycle and invasive potential of various human and live stock pathogens as well as major allergens. Therefore, this protease class is rigorously studied and requires sufficient amounts of protease protein to analyze structure-activity relationships, their 3-D structures as well as to screen for and optimize potent and selective inhibitors. This review summarizes approaches to generate active papain-like cysteine proteases by heterologous expression in a variety of expression systems.
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http://dx.doi.org/10.1016/s1046-2023(03)00212-3 | DOI Listing |
Mol Plant Pathol
January 2025
Fujian Key Laboratory of Plant Virology, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou, China.
The begomoviral V2 protein is known to be multifunctional, including its interaction with and inhibition of CYP1, a papain-like cysteine protease (PLCP). However, the effect of this interaction on viral pathogenicity remains unclear. Cotton leaf curl Multan virus (CLCuMuV), a typical monopartite begomovirus associated with a betasatellite, is one of the main pathogens responsible for cotton leaf curl disease.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Institute of Forest Biotechnology, Forestry College, Agricultural University of Hebei, Baoding 071000, China; Hebei Key Laboratory for Tree Genetic Resources and Forest Protection, Baoding 071000, China. Electronic address:
Papain-like cysteine proteases (PLCPs) are a large class of proteolytic enzymes involved in plant growth and development as well as plant responses to biological and abiotic stresses. However, there is no detailed characterization of PLCPs genes in poplar. In this study, a genome-wide analysis of the poplar PtrPLCPs family revealed 47 PtrPLCPs, which were classified into nine subfamilies according to their phylogeny: RD21, CEP, XCP, XBCP3, SAG12, RD19 (5), ALP, CTB, and the lost THI subgroups.
View Article and Find Full Text PDFJ Exp Bot
December 2024
The Plant Chemetics Laboratory, Department of Biology, University of Oxford, OX1 3RB Oxford, UK.
Over the past decades, numerous studies have demonstrated that proteases serve as a crucial regulatory mechanism in controlling plant immunity. In this review, we specifically focus on the role of one subfamily of RD21-like papain-like cysteine proteases that carry a C-terminal granulin domain. These proteases share high homology but have been described under very different names in different plant species.
View Article and Find Full Text PDFPlant Physiol Biochem
December 2024
Institute of Ecology and Environmental Sciences of Paris (iEES Paris), Univ Paris Est Creteil, CNRS, INRAE, IRD, IEES, F-94010, Creteil, France. Electronic address:
Current background tropospheric ozone (O) concentrations have significant adverse effects on wheat. O generally induces oxidative damages and premature leaf senescence leading to important yield losses. As leaf protein degradation and recycling is involved in both maintaining cell longevity during abiotic stresses and performing efficient nitrogen remobilization during senescence, we aimed to identify proteases involved in acidic endoproteolytic activities during natural and O-induced leaf senescence in wheat.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Competence Center for Drug Discovery, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences ZHAW, Wädenswil, Switzerland.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like cysteine protease (PLpro) represents one of only two essential cysteine proteases involved in the regulation of viral replication. It, therefore, qualifies as a promising therapeutic target for the development of antiviral agents. We identified a previously synthesized protease inhibitor, resulting from an earlier project, as a PLpro inhibitor and crafted a structure-activity relationship around the hit, leading to the more potent inhibitors ZHAWOC6941 (17h) and ZHAWOC25153 (17o) displaying IC values of 8 and 7 µM, respectively.
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