In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host
Proteolytic enzymes of the caspase family, which reside as latent precursors in most nucleated metazoan cells, are core effectors of apoptosis. Of them, the executioner caspases- 3 and -7 exist within the cytosol as inactive dimers and are activated by a process called dimerization. Caspase inhibiti...
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Biomedical Informatics
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705615/ |
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pubmed-37056152013-07-11 In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host Kumar, Shakti Biswal, Devendra Kumar Tandon, Veena Hypothesis Proteolytic enzymes of the caspase family, which reside as latent precursors in most nucleated metazoan cells, are core effectors of apoptosis. Of them, the executioner caspases- 3 and -7 exist within the cytosol as inactive dimers and are activated by a process called dimerization. Caspase inhibition is looked upon as a promising approach for treating multiple diseases. Though caspases have been extensively studied in the human system, their role in eukaryotic pathogens and parasites of human hosts has not drawn enough attention. In protein sequence analysis, caspases of blood flukes (Schistosoma spp) were revealed to have a low sequence identity with their counterparts in human and other mammalian hosts, which encouraged us to analyse interacting domains that participate in dimerization of caspases in the parasite and to reveal differences, if any, between the host-parasite systems. Significant differences in the molecular surface arrangement of the dimer interfaces reveal that in schistosomal caspases only eight out of forty dimer conformations are similar to human caspase structures. Thus, the parasite-specific dimer conformations (that are different from caspases of the host) may emerge as potential drug targets of therapeutic value against schistosomal infections. Three important factors namely, the size of amino acids, secondary structures and geometrical arrangement of interacting domains influence the pattern of caspase dimer formation, which, in turn, is manifested in varied structural conformations of caspases in the parasite and its human hosts. Biomedical Informatics 2013-05-25 /pmc/articles/PMC3705615/ /pubmed/23847399 http://dx.doi.org/10.6026/97320630009456 Text en © 2013 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kumar, Shakti Biswal, Devendra Kumar Tandon, Veena |
| spellingShingle |
Kumar, Shakti Biswal, Devendra Kumar Tandon, Veena In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| author_facet |
Kumar, Shakti Biswal, Devendra Kumar Tandon, Veena |
| author_sort |
Kumar, Shakti |
| title |
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| title_short |
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| title_full |
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| title_fullStr |
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| title_full_unstemmed |
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host |
| title_sort |
in-silico analysis of caspase-3 and -7 proteases from blood-parasitic schistosoma species (trematoda) and their human host |
| description |
Proteolytic enzymes of the caspase family, which reside as latent precursors in most nucleated metazoan cells, are core effectors of
apoptosis. Of them, the executioner caspases- 3 and -7 exist within the cytosol as inactive dimers and are activated by a process
called dimerization. Caspase inhibition is looked upon as a promising approach for treating multiple diseases. Though caspases
have been extensively studied in the human system, their role in eukaryotic pathogens and parasites of human hosts has not drawn
enough attention. In protein sequence analysis, caspases of blood flukes (Schistosoma spp) were revealed to have a low sequence
identity with their counterparts in human and other mammalian hosts, which encouraged us to analyse interacting domains that
participate in dimerization of caspases in the parasite and to reveal differences, if any, between the host-parasite systems.
Significant differences in the molecular surface arrangement of the dimer interfaces reveal that in schistosomal caspases only eight
out of forty dimer conformations are similar to human caspase structures. Thus, the parasite-specific dimer conformations (that are
different from caspases of the host) may emerge as potential drug targets of therapeutic value against schistosomal infections.
Three important factors namely, the size of amino acids, secondary structures and geometrical arrangement of interacting domains
influence the pattern of caspase dimer formation, which, in turn, is manifested in varied structural conformations of caspases in the
parasite and its human hosts. |
| publisher |
Biomedical Informatics |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705615/ |
| _version_ |
1611993202532810752 |