CPDB: cysteine protease annotation database in<i>Leishmania</i>species

Rana, Sindhuprava; Dikhit, Manas Ranjan; Rani, Mukta; Moharana, Kanhu C.; Sahoo, Ganesh Chandra; Das, Pradeep

doi:10.1039/c2ib20131c

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…The cysteine proteases in Leishmania exist in the gene families CPA, CPB, and CPC. It has been established that at least two of the families need to be targeted to absolutely block the parasite invasion and replication in host cells . In an effort to find new starting points for cysteine protease inhibitors, L. mexicana cysteine protease CPB2.8, which shows significant differences with bovine cathepsin B, was selected as a target.…”

Section: Drug Discovery For Leishmaniasismentioning

confidence: 80%

“…It has been established that at least two of the families need to be targeted to absolutely block the parasite invasion and replication in host cells. 272 In an effort to find new starting points for cysteine protease inhibitors, L. mexicana cysteine protease CPB2.8, which shows significant differences with bovine cathepsin B, was selected as a target. High throughput screening of a compound library against this enzyme and bovine cathepsin B (BtCatB) identified four novel inhibitor classes broadly classified into 3 groups depending on the warhead-types, namely thiosemicarbazones (118, 119), nitriles ( 120 ), and semicarbazones ( 121 ) (Figure 18 ).…”

Section: Drug Discovery For Leishmaniasismentioning

confidence: 99%

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Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

et al. 2014

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Section: Drug Discovery For Leishmaniasismentioning

confidence: 80%

Section: Drug Discovery For Leishmaniasismentioning

confidence: 99%

Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

et al. 2014

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“…LeishDB ( 46 ) included coding genes and non-RNAs and provided new annotation to them. The cysteine protease database in Leishmania species ( 47 ) was designed to find data related to cysteine protease and LeishBase ( 48 ) was a structural database. There are a few active databases: Leish-ExP ( http://www.hpppi.iicb.res.in/Leish-ex ) (which has not so far been published in a peer-reviewed journal) contains proteins exclusively present in Leishmania .…”

Section: Discussionmentioning

confidence: 99%

LeishMANIAdb: a comparative resource for Leishmania proteins

Tusnády,

Zeke,

Kálmán

et al. 2023

Database

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Leishmaniasis is a detrimental disease causing serious changes in quality of life and some forms can lead to death. The disease is spread by the parasite Leishmania transmitted by sandfly vectors and their primary hosts are vertebrates including humans. The pathogen penetrates host cells and secretes proteins (the secretome) to repurpose cells for pathogen growth and to alter cell signaling via host–pathogen protein–protein interactions). Here, we present LeishMANIAdb, a database specifically designed to investigate how Leishmania virulence factors may interfere with host proteins. Since the secretomes of different Leishmania species are only partially characterized, we collated various experimental evidence and used computational predictions to identify Leishmania secreted proteins to generate a user-friendly unified web resource allowing users to access all information available on experimental and predicted secretomes. In addition, we manually annotated host–pathogen interactions of 211 proteins and the localization/function of 3764 transmembrane (TM) proteins of different Leishmania species. We also enriched all proteins with automatic structural and functional predictions that can provide new insights in the molecular mechanisms of infection. Our database may provide novel insights into Leishmania host–pathogen interactions and help to identify new therapeutic targets for this neglected disease. Database URL https://leishmaniadb.ttk.hu/

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“…Of the cysteine proteases identified in H. contortus, family C01 contains the largest number of proteins-a total of 84 (see Section 2.2). C01 proteases are known for their diverse functions in protein-turnover, antigen processing, apoptosis, inflammation and pathogenesis [104][105][106]. One of the significant characteristics of C01 proteases in parasites is their high degree of diversity [107,108].…”

Section: Key Protease Gene Families Associate With Key Biological Fun...mentioning

confidence: 99%

Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions

Zheng,

Young,

Song

et al. 2023

IJMS

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Biodiversity within the animal kingdom is associated with extensive molecular diversity. The expansion of genomic, transcriptomic and proteomic data sets for invertebrate groups and species with unique biological traits necessitates reliable in silico tools for the accurate identification and annotation of molecules and molecular groups. However, conventional tools are inadequate for lesser-known organismal groups, such as eukaryotic pathogens (parasites), so that improved approaches are urgently needed. Here, we established a combined sequence- and structure-based workflow system to harness well-curated publicly available data sets and resources to identify, classify and annotate proteases and protease inhibitors of a highly pathogenic parasitic roundworm (nematode) of global relevance, called Haemonchus contortus (barber’s pole worm). This workflow performed markedly better than conventional, sequence-based classification and annotation alone and allowed the first genome-wide characterisation of protease and protease inhibitor genes and gene products in this worm. In total, we identified 790 genes encoding 860 proteases and protease inhibitors representing 83 gene families. The proteins inferred included 280 metallo-, 145 cysteine, 142 serine, 121 aspartic and 81 “mixed” proteases as well as 91 protease inhibitors, all of which had marked physicochemical diversity and inferred involvements in >400 biological processes or pathways. A detailed investigation revealed a remarkable expansion of some protease or inhibitor gene families, which are likely linked to parasitism (e.g., host–parasite interactions, immunomodulation and blood-feeding) and exhibit stage- or sex-specific transcription profiles. This investigation provides a solid foundation for detailed explorations of the structures and functions of proteases and protease inhibitors of H. contortus and related nematodes, and it could assist in the discovery of new drug or vaccine targets against infections or diseases.

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CPDB: cysteine protease annotation database inLeishmaniaspecies

Abstract: the database is available for free at.

Cited by 7 publications

References 34 publications

Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

LeishMANIAdb: a comparative resource for Leishmania proteins

Genome-Wide Analysis of Haemonchus contortus Proteases and Protease Inhibitors Using Advanced Informatics Provides Insights into Parasite Biology and Host–Parasite Interactions

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