Towards Tricking a Pathogen’s Protease into Fighting Infection: The 3D Structure of a Stable Circularly Permuted Onconase Variant Cleavedby HIV-1 Protease
dc.contributor.author
dc.date.accessioned
2013-02-26T15:36:17Z
dc.date.available
2013-02-26T15:36:17Z
dc.date.issued
2013-01
dc.identifier.uri
dc.description.abstract
Onconase® is a highly cytotoxic amphibian homolog of Ribonuclease A. Here, we describe the construction of circularly permuted Onconase® variants by connecting the N- and C-termini of this enzyme with amino acid residues that are recognized and cleaved by the human immunodeficiency virus protease. Uncleaved circularly permuted Onconase® variants are unusually stable, non-cytotoxic and can internalize in human T-lymphocyte Jurkat cells. The structure, stability and dynamics of an intact and a cleaved circularly permuted OnconaseH variant were determined by Nuclear Magnetic Resonance spectroscopy and provide valuable insight into the changes in catalytic efficiency caused by the cleavage. The understanding of the structural environment and the dynamics of the activation process represents a first step toward the development of more effective drugs for the treatment of diseases related to pathogens expressing a specific protease. By taking advantage of the protease’s activity to initiate a cytotoxic cascade, this approach is thought to be less susceptible to known resistance mechanisms
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.relation.isformatof
Reproducció digital del document publicat a: http://dx.doi.org/10.1371/journal.pone.0054568
dc.relation.ispartof
PloS ONE, 2013, vol. 8, núm. 1, p. e54568
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Articles publicats (D-B)
dc.rights
Attribution 2.5 Spain
dc.rights.uri
dc.title
Towards Tricking a Pathogen’s Protease into Fighting Infection: The 3D Structure of a Stable Circularly Permuted Onconase Variant Cleavedby HIV-1 Protease
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
017122
dc.identifier.eissn
1932-6203