Proteolytic Enzymes and Their Inhibitors in Infectious Pathogens

Auteur

Professor Theresa Coetzer's research focusses on proteolytic enzymes as diagnostic and drug targets in African parasitic diseases: mainly animal and human trypanosomiasis (nagana and sleeping sickness) and also trichinellosis and theileriosis. She also has expertise in producing antibodies in chickens against the whole proteases and against peptides corresponding to epitopes identified in silico. Dr. Coetzer holds a DST-NRF South African Research Chair Initiative (SARChI), as Chair in Proteolysis in Haemostasis, Health and Disease.

Texte du rabat

Proteolytic enzymes are found in all life forms, where they catalyze peptide bond hydrolysis during essential biological processes. Proteases of various pathogens have also been shown to use endogenous protease inhibitors to regulate the activity of host proteolytic enzymes encountered during infection.

Proteolytic Enzymes and their Inhibitors in Infectious Pathogens brings together key experts to provide a thorough discussion of proteolytic enzymes and their endogenous inhibitors found in parasites, bacteria, and viruses. The book focuses on the respective roles of the different catalytic classes of proteolytic enzymes and their protein-protease inhibitors at the host-infectious organism interface, and how this knowledge may inform drug and vaccine design. Following a foundational overview of proteases and macromolecular inhibitors of pathogenic organisms, authors discuss recent research on distinct classes of proteolytic enzymes in pathogens. Classes include aspartic proteases, cysteine proteases, metalloproteases, serine proteases, and threonine proteases with experts contributing chapters on distinct enzymes and inhibitors. New methods to identify protease substrates and inhibitors are also provided, with step-by-step protocols to advance new research and drive drug discovery.

Contenu

Part 1: Introduction
1. Overview of proteases of pathogenic organisms

2. Introducing endogenous macromolecular protease inhibitors of pathogenic organisms

Part 2: New methods to identify protease substrates and inhibitors

3. DNA-linked inhibitor antibody assay (DIANA) to capture proteases in complex mixtures and identify novel small-molecule inhibitors
4. New advances in positional proteomics strategies to study protein processing
5. Bioinformatics approaches for accurate prediction of protease-specific substrates and their cleavage sites
6. Delineating peptidase specificities at the host-parasite interface using Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS)
7. Recent Advances in Applications of Proteomic Approaches and Chemical Tools for Pathogen Profiling
8. Methods for mapping the mutational landscape of virus protease inhibitor binding sites to predict drug resistance

Part 3: Aspartic proteases and their inhibitors

9. Bacterial signal peptidases
10. Plasmepsins of the malaria parasite Plasmodium
11. Aspartic proteases of kinetoplasts
12. HIV1 subtype C protease hinge region dynamics and flap flexibility in drug resistance
13. Aspartic protease inhibitors of nematodes

Part 4: Cysteine proteases and their inhibitors
14. Polyprotein processing in SARS Cov-2

15. Gingipains of Porphyromonas gingivalis deactivators of innate immune and inflammatory defense mechanisms
16. Sortases in pilus biogenesis of Gram-positive bacteria
17. Cysteine proteases of protozoa
18. Multifunctional Nidovirus papain-like proteases
19. Chagasins: Inhibitors of Cysteine Proteases in Protozoa
20. Targeting the 3C-like proteases of Picornaviruses, Noroviruses, and Coronaviruses

Part 5: Metalloproteases and their inhibitors

21. The FusC about proteases involved in microbial iron piracy
22. Metallo-aminopeptidases in parasites and bacteria

Part 6: Serine proteases and their inhibitors

23. Oligopeptidase B popping up in many pathogens as a virulence factor
24. Ecotins of bacteria and protozoa
25. Serpins of trematodes and nematodes
26. Flaviviral serine NS2B-NS3 endoproteases

Part 7: Threonine proteases

27. Proteasome in Plasmodium and kinetoplast parasites
28. Proteasome in infectious organisms