Cysteine Proteases Inhibitors with Immunoglobulin-Like Fold in Protozoan Parasites and their Role in Pathogenesis

Jiménez‐Sandoval, Pedro; Lopez‐Castillo, Laura Margarita; Trasviña-Arenas, Carlos H.; Brieba, Luis G.

doi:10.2174/1389203717666160813163837

Cited by 4 publications

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“…In addition, cysteine proteases with molecular weights of 43, 65, 70, and 130 kDa have also been reported ( Khan, 2006 ). Although the histolytic role of cysteine proteases in the pathogenesis of parasitic pathogens has been identified ( Singh et al, 2004 ; Jimenez-Sandoval et al, 2017 ), the studies on cysteine proteases in Acanthamoeba are limited.…”

Section: Acanthamoeba Related Diseasesmentioning

confidence: 99%

Biological characteristics and pathogenicity of Acanthamoeba

et al. 2023

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Acanthamoeba is an opportunistic protozoa, which exists widely in nature and is mainly distributed in soil and water. Acanthamoeba usually exists in two forms, trophozoites and cysts. The trophozoite stage is one of growth and reproduction while the cyst stage is characterized by cellular quiescence, commonly resulting in human infection, and the lack of effective monotherapy after initial infection leads to chronic disease. Acanthamoeba can infect several human body tissues such as the skin, cornea, conjunctiva, respiratory tract, and reproductive tract, especially when the tissue barriers are damaged. Furthermore, serious infections can cause Acanthamoeba keratitis, granulomatous amoebic encephalitis, skin, and lung infections. With an increasing number of Acanthamoeba infections in recent years, the pathogenicity of Acanthamoeba is becoming more relevant to mainstream clinical care. This review article will describe the etiological characteristics of Acanthamoeba infection in detail from the aspects of biological characteristic, classification, disease, and pathogenic mechanism in order to provide scientific basis for the diagnosis, treatment, and prevention of Acanthamoeba infection.

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Section: Acanthamoeba Related Diseasesmentioning

confidence: 99%

Biological characteristics and pathogenicity of Acanthamoeba

et al. 2023

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“…However, in addition to these degradation functions, proteases act as sharp scissors and catalyze highly specific reactions of proteolytic processing, resulting in new peptides/protein products [ 1 ]. Moreover, proteases play a critical role in many biological, physiological and pathophysiological processes in the majority of unicellular and multicellular parasites [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Roles of Cysteine Proteases in Biology and Pathogenesis of Parasites

2023

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Cysteine proteases, also known as thiol proteases, are a class of nucleophilic proteolytic enzymes containing cysteine residues in the enzymatic domain. These proteases generally play a pivotal role in many biological reactions, such as catabolic functions and protein processing, in all living organisms. They specifically take part in many important biological processes, especially in the absorption of nutrients, invasion, virulence, and immune evasion of parasitic organisms from unicellular protozoa to multicellular helminths. They can also be used as parasite diagnostic antigens and targets for gene modification and chemotherapy, as well as vaccine candidates, due to their species and even life-cycle stage specificity. This article highlights current knowledge on parasitic cysteine protease types, biological functions, and their applications in immunodiagnosis and chemotherapy.

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“…Domains with an Ig-like fold are found in many proteins that are not antibodies. For instance, the outer membrane protein of the genus Leptospira (LigB), 17 type III domain of human fibronectin (FN3 domain), 18 and inhibitors of cysteine proteases (ICPs) from the MER-OPS family I42 [19][20][21][22][23] among many others. The most remarkable example of a PA with an Ig-fold is the FN3 domain.…”

Section: Introductionmentioning

confidence: 99%

“…16,35 ICPs also bear resemblance to the structure of the Ig-like domain of the human T cell co-receptor CD8a that can recognize a broad range of peptides. 22,31,32 Based on its structural properties we postulate that ICPs would be a proper scaffold to be used as a PA. 19 To mimic the interface between p53 and MDM2, we selected a synthetic peptide that resembles a part of the transactivation domain (a-helical) of p53 which is target of MDM2, and is able to form a MDM2-complex with very high affinity. 33 This sequence (N-TSFAEYWNLLSP) was independently grafted in each EhICP1 loop to generate 3 possible binding chimeras against MDM2.…”

Section: Introductionmentioning

confidence: 99%

Mimicking a p53‐MDM2 interaction based on a stable immunoglobulin‐like domain scaffold

et al. 2018

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Antibodies recognize protein targets with great affinity and specificity. However, posttranslational modifications and the presence of intrinsic disulfide-bonds pose difficulties for their industrial use. The immunoglobulin fold is one of the most ubiquitous folds in nature and it is found in many proteins besides antibodies. An example of a protein family with an immunoglobulin-like fold is the Cysteine Protease Inhibitors (ICP) family I42 of the MEROPs database for protease and protease inhibitors. Members of this protein family are thermostable and do not present internal disulfide bonds. Crystal structures of several ICPs indicate that they resemble the Ig-like domain of the human T cell co-receptor CD8α As ICPs present 2 flexible recognition loops that vary accordingly to their targeted protease, we hypothesize that members of this protein family would be ideal to design peptide aptamers that mimic protein-protein interactions. Herein, we use an ICP variant from Entamoeba histolytica (EhICP1) to mimic the interaction between p53 and MDM2. We found that a 13 amino-acid peptide derived from p53 can be introduced in 2 variable loops (DE, FG) but not the third (BC). Chimeric EhICP1-p53 form a stable complex with MDM2 at a micromolar range. Crystal structure of the EhICP1-p53(FG)-loop variant in complex with MDM2 reveals a swapping subdomain between 2 chimeric molecules, however, the p53 peptide interacts with MDM2 as in previous crystal structures. The structural details of the EhICP1-p53(FG) interaction with MDM2 resemble the interaction between an antibody and MDM2.

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Cysteine Proteases Inhibitors with Immunoglobulin-Like Fold in Protozoan Parasites and their Role in Pathogenesis

Cited by 4 publications

References 0 publications

Biological characteristics and pathogenicity of Acanthamoeba

Biological characteristics and pathogenicity of Acanthamoeba

Roles of Cysteine Proteases in Biology and Pathogenesis of Parasites

Mimicking a p53‐MDM2 interaction based on a stable immunoglobulin‐like domain scaffold

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