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Chagas’ Disease
Published in F. Y. Liew, Vaccination Strategies of Tropical Diseases, 2017
Johnson et al.80 tested in mice the protective effects of prior infection with Leptomonas collosoma, Crithidia fasciculata, T. mega and T. melophagium. Data were not provided but the statement was made that protection against T. cruzi was observed in all cases, although to a lesser degree with the latter two organisms.
23S rRNA-Derived Small Ribosomal RNAs: Their Structure and Evolution with References to Plant Phylogeny
Published in S. K. Dutta, DNA Systematics, 2019
Helix C is seen in all the known 5.8S rRNA and consists of five to eight complementary basepairs. The comparison of the secondary structure model with aligned nucleotide sequences shows that there exists a helical “nucleus”. This is formed, in various species, by homologous nucleotide residues. The ends of the helix in various species may shift from both sides of the nucleus, so that the corresponding homologous residues may in some species be contained in the helix, and in the others may remain in the unpaired state. In the E. coli 23S rRNA, the folding of a corresponding region into a helix is impossible. Based on structural mapping data of mammalian35,126,127 and fungal Thermomyces lanuginosus124 5.8S rRNA, Olsen and Sogin144 suggested that helix C was not present in vivo. Neither is the state of the nucleotide residues corresponding to chain B′ and the 3′ end of loop I determined unequivocally. According to the model of Walker et al.,126 this region in the free 5.8S rRNA is single-stranded, and in Nazar’s model35 B′ is included in the helical region. Helix B may be formed as an alternative to the “burp-gun” model pairing, with the 3′ end segment of loop I being involved (Figures 5 and 9). For Anemia salina 5.8S rRNA, a fit structure may be built only by this second method.93 The variant of the generalized secondary structure model proposed by Ursi et al.93,136 differs from Nazar’s model35 by the substitution of inner loop for bulge (Figure 5). Ursi et al.93 calculated the free energy of 5.8S rRNA secondary structure formation for their own model and that of Nazar (Table 2). It should be noted that Nazar’s model has an evident advantage for higher plant 5.8S rRNA and the model of Ursi et al. for protozoan 5.8S rRNA. For the Xenopus and yeast 5.8S rRNAs, both variants are almost energetically equivalent. For 5.8S rRNA Chlamydomonas reinhardii the energy of the secondary structure formation is positive in both cases, however, the Ursi variant is somewhat preferable. Arm F-VI, the so-called “GC-rich” hairpin, is revealed in all 5.8S rRNA, as well as in the homologous region of the E. coli 23S rRNA (Figure 10). The paradox consists in that this most universal structural element is at the same time the most variable region of the molecule both in the size of the helix and in the nucleotide sequence. Helix F contains, in various species, 7 to 11 bp. In fungi, vertebrates, several invertebrates, protozoans, and E. coli, helix has no defects; in other species it contains several looped-out bases. In the D. discoideum 5.8S rRNA, helix F is elongated through extending of pairing into chains A″ and B″. In the protozoan Crithidia fasciculata, this helix is somewhat longer due to insertion. In insects with a nicked 5.8S rRNA (Drosophila melanogaster and Sciara coprophila), helix F forms due to intermolecular interaction between 5.8Sa and 5.8Sb rRNA88,89 (Figure 2).
Mechanistic and biological characterisation of novel N 5-substituted paullones targeting the biosynthesis of trypanothione in Leishmania
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Andrea Medeiros, Diego Benítez, Ricarda S. Korn, Vinicius C. Ferreira, Exequiel Barrera, Federico Carrión, Otto Pritsch, Sergio Pantano, Conrad Kunick, Camila I. de Oliveira, Oliver C. F. Orban, Marcelo A. Comini
The kinetic and thermodynamic studies strongly suggest that the binding site of MOL2008 and 20, at least partially, overlaps with that of SP and GSP. GspS is an enzyme capable to catalyse the formation of GSP but not of T(SH)2 due to steric effects that preclude binding of GSP to the enzyme’s active site36. Thus, we reasoned that if occupation of the GSP-binding site by N5-substituted paullones is relevant for TryS inhibition, then GspS should not be inhibited by these compounds. Confirming our hypothesis, GspS from the Kinetoplastid Crithidia fasciculata proved refractory to MOL2008, which caused a minor inhibition (20%) of the enzyme at the highest concentration tested of 300 µM (see Supplementary Information for details about protein preparation and enzymatic assay). This concentration is 2000-fold higher than that needed to produce 50% inhibition of LiTryS (Table 1).