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Functional characterization of a SUMO deconjugating protease of Plasmodium falciparum using newly identified small molecule inhibitors.
- Source :
-
Chemistry & biology [Chem Biol] 2011 Jun 24; Vol. 18 (6), pp. 711-21. - Publication Year :
- 2011
-
Abstract
- Small ubiquitin-related modifier (SUMO) is implicated in the regulation of numerous biological processes including transcription, protein localization, and cell cycle control. Protein modification by SUMO is found in Plasmodium falciparum; however, its role in the regulation of the parasite life cycle is poorly understood. Here we describe functional studies of a SUMO-specific protease (SENP) of P. falciparum, PfSENP1 (PFL1635w). Expression of the catalytic domain of PfSENP1 and biochemical profiling using a positional scanning substrate library demonstrated that this protease has unique cleavage sequence preference relative to the human SENPs. In addition, we describe a class of small molecule inhibitors of this protease. The most potent lead compound inhibited both recombinant PfSENP1 activity and P. falciparum replication in infected human blood. These studies provide valuable new tools for the study of SUMOylation in P. falciparum.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Catalytic Domain
Cysteine Endopeptidases
Endopeptidases metabolism
Humans
Hydrazines chemistry
Molecular Sequence Data
Phthalic Acids chemistry
Protease Inhibitors chemistry
Protozoan Proteins classification
Protozoan Proteins genetics
Recombinant Proteins antagonists & inhibitors
Recombinant Proteins genetics
Recombinant Proteins metabolism
Substrate Specificity
Hydrazines pharmacology
Phthalic Acids pharmacology
Plasmodium falciparum enzymology
Protease Inhibitors pharmacology
Protozoan Proteins chemistry
Small Ubiquitin-Related Modifier Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1301
- Volume :
- 18
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Chemistry & biology
- Publication Type :
- Academic Journal
- Accession number :
- 21700207
- Full Text :
- https://doi.org/10.1016/j.chembiol.2011.04.010