Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017536 (giardiasis)
 1,714 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The parasite Giardia intestinalis undergoes a differentiation process that allows it to infect its mammal host. That process is excystation. We examined the importance of protein phosphorylation during the passage from cyst to trophozoite. Cysts obtained from patients with giardiasis were excysted in vitro and the soluble cytoplasmic proteins were analyzed during the three phases of the process, using a specific staining for phosphoproteins. We found two phosphorylated proteins and identified them with MALDI-TOF as 14-3-3 and Hsp70. Modifications were detected in both proteins, which could indicate a role in differentiation of the parasite. In addition, the inhibition of serine-threonine kinases during excystation specifically affected the cytokinesis of the excyzoite, thus inhibiting the completion of trophozoite formation.
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PMID:Analysis of phosphorylated proteins and inhibition of kinase activity during Giardia intestinalis excystation. 1986 Nov 70

14-3-3s are phosphoserine/phosphotreonine binding proteins that play pivotal roles as regulators of multiple cellular processes in eukaryotes. The flagellated protozoan parasite Giardia duodenalis, the causing agent of giardiasis, is a valuable simplified eukaryotic model. A single 14-3-3 isoform (g14-3-3) is expressed in Giardia, and it is directly involved in the differentiation of the parasite into cyst. To define the overall functions of g14-3-3, the protein interactome has been investigated. A transgenic G. duodenalis strain was engineered to express a FLAG-tagged g14-3-3 under its own promoter. Affinity chromatography coupled with tandem mass spectrometry analysis have been used to purify and identify FLAG-g14-3-3-associated proteins from trophozoites and encysting parasites. A total of 314 putative g14-3-3 interaction partners were identified, including proteins involved in several pathways. Some interactions seemed to be peculiar of one specific stage, while others were shared among the different stages. Furthermore, the interaction of g14-3-3 with the giardial homologue of the CDC7 protein kinase (gCDC7) was characterized, leading to the identification of a multiprotein complex containing not only g14-3-3 and gCDC7 but also a newly identified and highly divergent homologue of DBF4, the putative regulatory subunit of gCDC7. The relevance of g14-3-3 interactions in G. duodenalis biology was discussed.
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PMID:Interaction network of the 14-3-3 protein in the ancient protozoan parasite Giardia duodenalis. 2245 40

Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan parasite Giardia duodenalis, which affects annually over 200 million people worldwide. The limited antigiardial drug arsenal and the emergence of clinical cases refractory to standard treatments dictate the need for new chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively involved in protein-protein interactions (PPIs) with pSer/pThr clients, represents a highly promising target. Despite homology with human counterparts, the single 14-3-3 of G. duodenalis (g14-3-3) is characterized by a constitutive phosphorylation in a region critical for target binding, thus affecting the function and the conformation of g14-3-3/clients interaction. However, to approach the design of specific small molecule modulators of g14-3-3 PPIs, structural elucidations are required. Here, we present a detailed computational and crystallographic study exploring the implications of g14-3-3 phosphorylation on protein structure and target binding. Self-Guided Langevin Dynamics and classical molecular dynamics simulations show that phosphorylation affects locally and globally g14-3-3 conformation, inducing a structural rearrangement more suitable for target binding. Profitable features for g14-3-3/clients interaction were highlighted using a hydrophobicity-based descriptor to characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in complex with a mode-1 prototype phosphopeptide was solved and combined with structure-based simulations to identify molecular features relevant for clients binding to g14-3-3. The data presented herein provide a further and structural understanding of g14-3-3 features and set the basis for drug design studies.
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PMID:Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions. 2655 37

Giardia duodenalis is a cosmopolitan zoonotic protozoan parasite causing giardiasis, one of the most common diarrhoeal diseases in human and animals. Beyond its public health relevance, Giardia represents a valuable and fascinating model microorganism. The deep-branching phylogenetic position of Giardia, its simple life cycle and its minimalistic genomic and cellular organization provide a unique opportunity to define basal and "ancestral" eukaryotic functions. The eukaryotic 14-3-3 protein family represents a distinct example of phosphoserine/phosphothreonine-binding proteins. The extended network of protein-protein interactions established by 14-3-3 proteins place them at the crossroad of multiple signalling pathways that regulate physiological and pathological cellular processes. Despite the remarkable insight on 14-3-3 protein in different organisms, from yeast to humans, so far little attention was given to the study of this protein in protozoan parasites. However, in the last years, research efforts have provided evidences on unique properties of the single 14-3-3 protein of Giardia and on its association in key aspects of Giardia life cycle. In the first part of this chapter, a general overview of the features commonly shared among 14-3-3 proteins in different organisms (i.e. structure, target recognition, mode of action and regulatory mechanisms) is included. The second part focus on the current knowledge on the biochemistry and biology of the Giardia 14-3-3 protein and on the possibility to use this protein as target to propose new strategies for developing innovative antigiardial therapy.
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PMID:The protein 14-3-3: A functionally versatile molecule in Giardia duodenalis. 3163 Jul 60