Protozoan parasite-specific carbohydrate structures

Mendonça-Previato, Lúcia; Todeschini, Adriane R.; Heise, Norton

doi:10.1016/j.sbi.2005.08.011

Cited by 61 publications

(47 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The parasitic protozoon has a simple life cycle: an infectious cystic form, which is ingested via contaminated water or food; and an invasive amoeboid trophozoite stage. Trophozoites are the motile forms with capacity to colonize and occasionally invade the colonic mucosa [2]. The cell surface of E. histolytica is decisive for recognition and killing of target host cells, with several molecules clearly identified for their involvement in amoebic pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

et al. 2011

View full text Add to dashboard Cite

a b s t r a c tAmoebiasis is an intestinal infection caused by the human pathogen Entamoeba histolytica and representing the third leading cause of death by parasites in the world. Host-parasite interactions mainly involve anchored glycoconjugates localized in the surface of the parasitic cell. In protozoa, synthesis of structural oligo-and polysaccharides occurs via UDP-glucose, generated in a reaction catalyzed by UDPglucose pyrophosphorylase. We report the molecular cloning of the gene coding for this enzyme from genomic DNA of E. histolytica and its recombinant expression in Escherichia coli cells. The purified enzyme was kinetically characterized, catalyzing UDP-glucose synthesis and pyrophosphorolysis with V max values of 95 U/mg and 3 U/mg, respectively, and affinity for substrates comparable to those found for the enzyme from other sources. Enzyme activity was affected by redox modification of thiol groups. Different oxidants, including diamide, hydrogen peroxide and sodium nitroprusside inactivated the enzyme. The process was completely reverted by reducing agents, mainly cysteine, dithiothreitol, and thioredoxin. Characterization of the enzyme mutants C94S, C108S, C191S, C354S, C378S, C108/378S, M106S and M106C supported a molecular mechanism for the redox regulation. Molecular modeling confirmed the role of specific cysteine and methionine residues as targets for redox modification in the entamoebic enzyme. Our results suggest that UDP-glucose pyrophosphorylase is a regulated enzyme in E. histolytica. Interestingly, results strongly agree with the occurrence of a physiological redox mechanism modulating enzyme activity, which would critically affect carbohydrate metabolism in the protozoon.

show abstract

Section: Introductionmentioning

confidence: 99%

“…E. histolytica displays a class of highly polymorphic glycosylphosphatidylinositol (GPI)-anchored cell-surface glycoconjugates, originally referred as lipophosphoglycans (LPGs). Antibodies against LPGs inhibit adhesion of trophozoites to mammalian cells, indicating that the antigen may be involved in hosteparasite interactions [1,2].…”

Section: Introductionmentioning

confidence: 99%

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

et al. 2011

View full text Add to dashboard Cite

show abstract

“…cruzi is controversial. In addition to the carbohydrate-binding site present in the catalytic pocket of the inactive TS implicated in the infectivity of the parasite (Mendonça- Previato et al 2005 ;Souza et al 2010 ;Rubin and Schenkman 2012 ), binding to cell receptors due to the lectin-like domain was also reported for TS, as the nerve growth factor receptor (Trk) (Chuenkova and Pereira Perrin 2005 ; de Melo-Jorge and Dias et al 2008 ;Weinkauf et al 2011 ). Notwithstanding, due to the high number of Gp85/TS proteins displaying extensive polymorphism, it is not unlikely that different members of the superfamily can perform different functions on a complex biological phenomenon, such as parasite adhesion to host cells.…”

Section: Grouping the Gp85/ts Gene Superfamily: General Structurementioning

confidence: 99%

The Gp85 Surface Glycoproteins from Trypanosoma cruzi

Mattos

Tonelli

Colli

et al. 2013

Subcellular Biochemistry

View full text Add to dashboard Cite

Trypanosoma cruzi strains show distinctive characteristics as genetic polymorphism and infectivity. Large repertoires of molecules, such as the Gp85 glycoproteins, members of the Gp85/Trans-sialidase superfamily, as well as multiple signaling pathways, are associated with invasion of mammalian cells by the parasite. Due to the large number of expressed members, encoded by more than 700 genes, the research focused on this superfamily conserved sequences is discussed. Binding sites to laminin have been identified at the N-terminus of the Gp85 molecules. Interestingly, the T. cruzi protein phosphorylation profile is changed upon parasite binding to laminin (or fibronectin), particularly the cytoskeletal proteins such as those from the paraflagellar rod and the tubulins, which are both markedly dephosphorylated. Detailed analysis of the signaling cascades triggered upon T. cruzi binding to extracellular matrix (ECM) proteins revealed the involvement of the MAPK/ERK pathway in this event. At the C-terminus, the conserved FLY sequence is a cytokeratin-binding domain and is involved in augmented host cell invasion in vitro and high levels of parasitemia in vivo. FLY, which is associated to tissue tropism and preferentially binds to the heart vasculature may somehow be correlated with the severe cardiac form, an important clinical manifestation of chronic Chagas' disease.

show abstract

“…Antiparasitische Impfstoffkandidaten ¾hnlich wie Bakterien synthetisieren auch viele Parasiten ungewçhnliche Glycokonjugate auf ihrer Oberfläche; diese sind oft immunogen und kçnnen als Zielstruktur für die Entwicklung antiparasitischer Impfstoffe dienen. [267] Plasmodium falciparum ist ein protozoischer Parasit, der für etwa 95 % der Malariatoten weltweit verantwortlich ist. [268] Die Proteinglycosylierung in Plasmodium geschieht zu 90 % hochkonserviert über die Kupplung eines GPI-Ankers, der als zentrales Parasitentoxin angesehen wird, da er die Produktion von proinflammatorischen Cytokinen und Stickoxid durch Makrophagen induziert und so zur Pathogenese von Malaria beiträgt.…”

Section: Nutzung Synthetischer Kohlenhydrate Für Die Impfstoffentwickunclassified

Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese

Hsu

Hung

et al. 2011

Angewandte Chemie

View full text Add to dashboard Cite

Kohlenhydrate spielen eine wichtige Rolle bei biologischen Vorgängen. Das Fortschrittstempo der Kohlenhydratforschung ist jedoch relativ langsam, was unter anderem mit der Komplexität der Kohlenhydratstrukturen und dem Fehlen allgemein anwendbarer Synthesemethoden und Verfahren zur Untersuchung dieser Klasse von Biomolekülen zusammenhängt. Jüngste Fortschritte in der Synthese haben ergeben, dass viele dieser Probleme umgangen werden können. In diesem Aufsatz beschreiben wir die Methoden, die entwickelt wurden, um mit den Herausforderungen kohlenhydratvermittelter biologischer Vorgänge umzugehen. Besonderes Augenmerk wird dabei auf die Entwicklung der automatisierten Synthese von Oligosacchariden gerichtet. Darüber hinaus werden auch Kohlenhydrat‐Mikroarrays und Impfstoffe auf Kohlenhydratbasis behandelt.

show abstract

Protozoan parasite-specific carbohydrate structures

Cited by 61 publications

References 36 publications

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

Redox regulation of UDP-glucose pyrophosphorylase from Entamoeba histolytica

The Gp85 Surface Glycoproteins from Trypanosoma cruzi

Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese

Contact Info

Product

Resources

About