Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously identified a Trypanosoma cruzi cDNA encoding a protein named Tc52 sharing structural and functional properties with the thioredoxin and glutaredoxin protein family involved in thiol-disulphide redox reactions. Furthermore, we reported that Tc52 also plays a role in T. cruzi-associated immunosuppression observed during Chagas' disease. Moreover, Tc52 gene targeting deletion strategy allowed us to demonstrate that monoallelic disruption of Tc52 resulted in the alteration of the metacyclogenesis process and the production of less virulent parasites. Sequence analysis of a 7358 bp genomic fragment containing the Tc52 encoding gene revealed two additional open reading frames (ORF-A and C). The ORFs are likely to have protein coding function by a number of criteria, including reverse transcriptase polymerase chain reaction (RT-PCR), Western blot and immunofluorescence analyses. The deduced amino-acid (aa) sequence of the ORF-A localized upstream of the Tc52 gene revealed that it contains within its N-terminus (aa 1 to 170) four RGG boxes known to act as RNA binding motifs in some proteins that interact with RNA, interspersed with a high density of glycine with regular spacing of tryptophan (WX(9-10)) in which X is often a glycine. Moreover, the C-terminal part of the ORF-C (aa 253-289) contains a motif that is strikingly similar (7-35% identity, 14-46% similarity over 28aa) to a short sequence (RNP1) comprising the consensus sequence RNA binding domain (CS-RBD) found in a number of proteins that interact with RNA. The aa sequence from the ORF-C localized downstream of the Tc52 gene showed significant homology to human adenosine deaminase acting on RNA (hADAT1) that specifically deaminates adenosine 37 to inosine in eukaryotic tRNA(Ala) and to its homologue yeast protein (Tad1p) (22-25% identity and an additional 38-40% similarity over 177aa). Moreover, highly similar motifs of the deaminase domain are present in the T. cruzi ORF-C. Furthermore, the 5' flanking regions of the genes contained repeat TATA and CAAT nucleotide sequences which resemble the motifs found upstream of the transcription initiation sites in eukaryotic promoters. Therefore, the characterization of novel T. cruzi genes encoding proteins which show similarity to components of RNA processing reactions provides new tools to investigate the gene expression regulation in these parasitic organisms. Moreover, our recent findings on the Tc52 encoding gene underline the interest of genetic manipulation of T. cruzi, not only making it possible to use more closely an in vitro approach to find out how genes function, but also to obtain 'attenuated' strains that could be used in the development of vaccinal strategies.
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PMID:Identification and molecular characterization of two novel Trypanosoma cruzi genes encoding polypeptides sharing sequence motifs found in proteins involved in RNA editing reactions. 1094 May 65

Hepatic stellate cells (HSC) play a crucial role in the development of liver fibrosis and are important targets in liver disease therapy. Adenosine acts as an extracellular signaling molecule in various tissues and in liver this nucleoside exerts protective effects. Ecto-5'-nucleotidase/CD73 is a marker for the plasma membrane and is considered to be a key enzyme in the generation of adenosine in the extracellular medium, by transforming AMP into adenosine. In addition, adenosine production from AMP is also catalyzed by alkaline phosphatase. We compared the extracellular metabolism of AMP and transcriptional levels of the ecto-5'-nucleotidase/CD73 and tissue non-specific alkaline phosphatase (TNALP) in activated and quiescent HSC of the mouse hepatic stellate cell line GRX. This cell line expresses a myofibroblast phenotype in basal medium and both retinol and indomethacin treatment induced a phenotypic change of GRX cells to quiescent HSC. Ecto-5'-nucleotidase activity and its mRNA expression were found to be higher in quiescent HSC than in activated HSC. During phenotype conversion, mediated by retinol, the AMP decay was accelerated with adenosine accumulation in extracellular medium, likely due to the decrease in adenosine deaminase activity also observed in quiescent HSC. The treatment with retinol also involves transcriptional activation of TNALP. Taken together, these data suggest that ecto-5'-nucleotidase-dependent adenosine generation may play a role in the regulation of quiescent HSC functions.
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PMID:Activity and expression of ecto-5'-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line. 1803 49