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Malaria is a global disease and a major health problem. The control of malaria is a daunting task due to the increasing drug resistance. Therefore, there is an urgent need to identify and characterize novel parasite specific drug targets. In the present study we report the biochemical characterization of parasite specific UvrD helicase from Plasmodium falciparum. The N-terminal fragment (PfUDN) containing UvrD helicase domain, which consists of helicase motifs Q, Ia-Id, II, III and most of motif IV, and the C-terminal fragment (PfUDC1) containing UvrD helicase C terminal domain, consisting of remaining part of motif IV and motifs IVa-IVc and 161 amino acids of intervening sequence between motif IV and V, possess ssDNA-dependent ATPase and DNA helicase activities in vitro. Using immunodepletion assays we show that the ATPase and helicase activities are attributable to PfUDN and PfUDC1 proteins. The helicase activity can utilize the hydrolysis of all the nucleotide and deoxynucleotide triphosphates and the direction of unwinding is 3' to 5'. The endogenous P. falciparum UvrD contains the characteristic DNA helicase activity. PfUDN interacts with PfMLH (P. falciparum MutL homologue) and modulates the endonuclease activity of PfMLH and PfMLH positively regulates the unwinding activity of PfUDN. We show that PfUvrD is expressed in the nucleus distinctly in the schizont stages of the intraerythrocytic development of the parasite and it colocalizes with PfMLH. These studies will make an important contribution in understanding the nucleic acid transaction in the malaria parasite.
Pubmed ID: 23185322
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Biomedical technology resource center that develops software and web-based resources for the visualization and analysis of molecular structure, and related data, at scales ranging from the atomic to the supramolecular. They create tools for handling and integrating diverse types of biomolecular data, including atomic-resolution coordinates, density maps, sequences, annotations, and networks. Their primary efforts are in the visualization and analysis of structures of molecules and molecular assemblies, enzyme sequence-structure-function relationships, and network representations of protein similarity, binding interactions, and biological pathways. They provide technologies to enable identifying the molecular bases of disease and phenotypic variation, annotating proteins of unknown function, identifying targets for drug development, designing drugs, and engineering proteins with new functions. RBVI distributes software tools, including the popular UCSF Chimera visualization and analysis package, develops and hosts the Structure-Function Linkage Database, and provides access to state-of-the-art computational resources in support of research projects in these areas.
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View all literature mentionsDatabase of protein families and domains that is based on the observation that, while there is a huge number of different proteins, most of them can be grouped, on the basis of similarities in their sequences, into a limited number of families. Proteins or protein domains belonging to a particular family generally share functional attributes and are derived from a common ancestor. It is complemented by ProRule, a collection of rules based on profiles and patterns, which increases the discriminatory power of profiles and patterns by providing additional information about functionally and/or structurally critical amino acids. ScanProsite finds matches of your protein sequences to PROSITE signatures. PROSITE currently contains patterns and profiles specific for more than a thousand protein families or domains. Each of these signatures comes with documentation providing background information on the structure and function of these proteins. The database is available via FTP.
View all literature mentionsA portal to biomedical and genomic information. NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease.
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View all literature mentionsDatabase of annotated three-dimensional comparative protein structure models generated by the fully automated homology-modelling pipeline SWISS-MODEL.
View all literature mentionsFunctional genomic database for malaria parasites. Database for Plasmodium spp. Provides resource for data analysis and visualization in gene-by-gene or genome-wide scale. PlasmoDB 5.5 contains annotated genomes, evidence of transcription, proteomics evidence, protein function evidence, population biology and evolution data. Data can be queried by selecting from query grid or drop down menus. Results can be combined with each other on query history page. Search results can be downloaded with associated functional data and registered users can store their query history for future retrieval or analysis.Key community database for malaria researchers, intersecting many types of laboratory and computational data, aggregated by gene.
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