The recognition of proteasomal receptors by Plasmodium falciparum DSK2

In this study, we have demonstrated how PfDsk2 and its recognition by proteasomal receptors differ from the mammalian system. Our crystal structure of unbound PfDsk2 UBL domain at 1.30 Å revealed an additional 310-helix compared to the human homolog, as well as a few significant differences in its putative binding interface with the proteasome receptors, PfRpn10 and PfRpn13. Moreover, the non-binding face of UBL showed a reversal of surface charge compared to HsDsk2 shuttle protein, instead resembling HOIL-like E3 ligase UBL domain. The affinity of the interaction with the proteasomal receptors remained similar to the human system, and dissociation constants of the same order of magnitude. On the other hand, we have found evidence of a novel interaction between PfRpn13DEUBAD with the PfDsk2UBL suggesting that PfDsk2 may work in cooperation with deubiquitinating enzymes for proofreading ubiquitinated substrates. Our study provides the first molecular look at shuttle proteins in Apicomplexan parasites and hints at how their interaction landscape might be broader than what we may expect.Graphical abstract
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research

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Conclusion: CoBaT-Y017, a Phase II study was conducted with Plasmodium falciparum malaria-infected patients, for efficacy and safety evaluation of CoBaT-Y017 compared with Artemether-Lumefantrine used as a positive control. Methods. A single-blind randomized trial was conducted on 25 eligible males aged 18-40 years randomly assigned to two treatment groups: CoBaT-Y017 or Artemether-Lumefantrine. The first group received 35 ml of CoBaT-Y017 in 1.5 L mineral water administered daily for four consecutive days; the second group received oral Artemether-Lumefantrine, using WHO-recommended therapeutic dose regimens...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Imperatore Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obta...
Source: Molecules - Category: Chemistry Authors: Tags: Communication Source Type: research
Progress made in the control of malaria vectors globally is largely due to the use of insecticides. However, success in the fight against malaria has slowed down or even stalled due to a host of factors includ...
Source: Parasites and Vectors - Category: Microbiology Authors: Tags: Research Source Type: research
AbstractMalaria is a major public health problem in tropical and subtropical countries of the World. During the year 1999, Visakhapatnam district of Andhra Pradesh, India experienced a major epidemic of malaria, and nearly 41,805 cases were reported. Hence, a retrospective malaria surveillance study was conducted from 2001 to 2016 and reported nearly a total of 149,317 malaria cases during the study period. Of which,Plasmodium vivax contributes 32%, andPlasmodium falciparum contributes 68% of the total cases. Malaria cases follow a strong seasonal variation and 70% of cases are reported during the monsoon periods. In the p...
Source: Journal of Parasitic Diseases - Category: Parasitology Source Type: research
Abstract Malaria etiologies with pathophysiological similarities to hypertension currently constitute a major subject of research. The malaria-high blood pressure hypothesis is strongly supported by observations of the increasing incidence of hypertension in malaria-endemic, low and middle-income countries (LMICs) with poor socio-economic conditions, particularly in sub-Saharan African countries. Malnutrition and low birth weight with persistent symptomatic malaria presentations in pregnancy correlate strongly with the development of preeclampsia, gestational hypertension and subsequent hypertension in adult life....
Source: American Journal of Hypertension - Category: Cardiology Authors: Tags: Am J Hypertens Source Type: research
The pore forming Plasmodium Perforin Like Proteins (PPLP), expressed in all stages of the parasite life cycle are critical for completion of the parasite life cycle. The high sequence similarity in the central Membrane Attack Complex/ Perforin (MACPF) domain among PLPs and their distinct functional overlaps define them as lucrative target for developing multi-stage antimalarial therapeutics. Herein, we evaluated the mechanism of Pan-active MACPF Domain (PMD), a centrally located and highly conserved region of PPLPs, and deciphered the inhibitory potential of specifically designed PMD inhibitors. The E. coli expressed rPMD ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Conclusions: We have identified five novel compounds with promising activities against N. caninum, the effects of three of these compounds were studies by transmission electron microscopy (TEM). Their modes of action are unknown and require further investigation.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
This study provides evidence supporting a role of RBP2-P1 as an invasion ligand and its consideration as a vaccine target.
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Fungal and Parasitic Infections Source Type: research
Development of a successful blood-stage vaccine against Plasmodium falciparum malaria remains a high priority. Immune-epidemiological studies are effective tools for the identification of antigenic targets of naturally acquired immunity (NAI) against malaria. However, differences in study design and methodology may compromise interstudy comparisons. Here, we assessed antibody responses against intact merozoites and a panel of 24 recombinant merozoite antigens in longitudinal cohort studies of Ghanaian (n = 115) and Indian (n = 121) populations using the same reagents and statistical methods. Anti-merozoite antibodies were ...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Fungal and Parasitic Infections Source Type: research
by Isobel Routledge, Shengjie Lai, Katherine E. Battle, Azra C. Ghani, Manuel Gomez-Rodriguez, Kyle B. Gustafson, Swapnil Mishra, Juliette Unwin, Joshua L. Proctor, Andrew J. Tatem, Zhongjie Li, Samir Bhatt In order to monitor progress towards malaria elimination, it is crucial to be able to measure changes in spatio-temporal transmission. However, common metrics of malaria transmission such as parasite prevalence are under powered in elimination contexts. China has achieved major reductions in malar ia incidence and is on track to eliminate, having reporting zero locally-acquired malaria cases in 2017 and 2018. Understan...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
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