Cysteine Proteases: Modes of Activation and Future Prospects as Pharmacological Targets.
Reads0
Chats0
TLDR
This review specifically highlights the modes of activation (processing) of papain family enzymes, which involve auto-activation, trans-activation and also clarifies the future aspects of targeting PPIs to prevent the activation of cysteine proteases.Abstract:
Proteolytic enzymes are crucial for a variety of biological processes in organisms ranging from lower (virus, bacteria, and parasite) to the higher organisms (mammals). Proteases cleave proteins into smaller fragments by catalyzing peptide bonds hydrolysis. Proteases are classified according to their catalytic site, and distributed into four major classes: cysteine proteases, serine proteases, aspartic proteases, and metalloproteases. This review will cover only cysteine proteases, papain family enzymes which are involved in multiple functions such as extracellular matrix turnover, antigen presentation, processing events, digestion, immune invasion, hemoglobin hydrolysis, parasite invasion, parasite egress, and processing surface proteins. Therefore, they are promising drug targets for various diseases. For preventing unwanted digestion, cysteine proteases are synthesized as zymogens, and contain a prodomain (regulatory) and a mature domain (catalytic). The prodomain acts as an endogenous inhibitor of the mature enzyme. For activation of the mature enzyme, removal of the prodomain is necessary and achieved by different modes. The pro-mature domain interaction can be categorized as protein–protein interactions (PPIs) and may be targeted in a range of diseases. Cysteine protease inhibitors are available that can block the active site but no such inhibitor available yet that can be targeted to block the pro-mature domain interactions and prevent it activation. This review specifically highlights the modes of activation (processing) of papain family enzymes, which involve auto-activation, trans-activation and also clarifies the future aspects of targeting PPIs to prevent the activation of cysteine proteases.read more
Citations
More filters
Journal ArticleDOI
Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.
Min Han Lin,David C. Moses,Chih Hua Hsieh,Shu Chun Cheng,Yau-Hung Chen,Chiao Yin Sun,Chi-Yuan Chou +6 more
TL;DR: It is shown that a clinically available alcohol‐aversive drug, disulfiram, can inhibit the papain‐like proteases (PLpros) of MERS‐CoV and SARS‐ coV, and the potential for combination treatments using these three clinically available drugs is implied.
Journal ArticleDOI
Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities.
TL;DR: Treatment intervention strategies for anti-SARS-CoV, MERS- coV, and other coronaviruses are highlighted and future directions for SARS- CoV-2 entry inhibitor designs are speculated upon.
Journal ArticleDOI
The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management.
TL;DR: The available evidence regarding the role of cathepsins in health and disease is summarized, their potential as biomarkers of disease progression is discussed, and light is shed on the potential of extracellularCathepsin inhibitors as safe therapeutic tools.
Journal ArticleDOI
Proteases and protease inhibitors in infectious diseases
TL;DR: This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions and assess the mechanism of action and clinical performance of the protease inhibitors against infectious agents.
Journal ArticleDOI
Amide Bond Activation of Biological Molecules
TL;DR: The methodologies for the activation of the unactivated amide bonds present in biomolecules are reported, which includes the enzymatic approach, metal complexes, and non-metal based methods.
References
More filters
Journal ArticleDOI
Cysteine cathepsins: From structure, function and regulation to new frontiers
TL;DR: The view of cysteine cathepsins as lysosomal proteases is changing as there is now clear evidence of their localization in other cellular compartments, and some of the remarkable advances that have taken place in the past decade are presented.
Journal ArticleDOI
Emerging roles for cysteine proteases in human biology
TL;DR: The ability of macrophages and other cells to mobilize elastolytic cysteine proteases to their surfaces under specialized conditions may also lead to accelerated collagen and elastin degradation at sites of inflammation in diseases such as atherosclerosis and emphysema.
Journal ArticleDOI
Hemoglobin metabolism in the malaria parasite Plasmodium falciparum.
TL;DR: Understanding the disposition of hemoglobin has allowed identification of essential processes and metabolic weakpoints that can be exploited to combat this scourge of mankind.
Journal ArticleDOI
Cysteine proteases of parasitic organisms
Mohammed Sajid,James H. McKerrow +1 more
TL;DR: In this paper, the authors highlight recent research on the Papain-like and asparaginyl-endopeptidase classes of cysteine proteases and re-examine them in light of the diversity uncovered within parasitic organisms.