| 1. |
- Gabrielsen, Mads, et al.
(author)
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Structural Characterisation of Tpx from Yersinia pseudotuberculosis Reveals Insights into the Binding of Salicylidene Acylhydrazide Compounds
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2, s. e32217-
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Journal article (peer-reviewed)abstract
- Thiol peroxidase, Tpx, has been shown to be a target protein of the salicylidene acylhydrazide class of antivirulence compounds. In this study we present the crystal structures of Tpx from Y. pseudotuberculosis (ypTpx) in the oxidised and reduced states, together with the structure of the C61S mutant. The structures solved are consistent with previously solved atypical 2-Cys thiol peroxidases, including that for “forced” reduced states using the C61S mutant. In addition, by investigating the solution structure of ypTpx using small angle X-ray scattering (SAXS), we have confirmed that reduced state ypTpx in solution is a homodimer. The solution structure also reveals flexibility around the dimer interface. Notably, the conformational changes observed between the redox states at the catalytic triad and at the dimer interface have implications for substrate and inhibitor binding. The structural data were used to model the binding of two salicylidene acylhydrazide compounds to the oxidised structure of ypTpx. Overall, the study provides insights into the binding of the salicylidene acylhydrazides to ypTpx, aiding our long-term strategy to understand the mode of action of this class of compounds.
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| 2. |
- McMillan, P. J, et al.
(author)
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Differential inhibition of high and low Mr thioredoxin reductases of parasites by organotelluriums supports the concept that low Mr thioredoxin reductases are good drug targets
- 2009
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In: Parasitology. - 0031-1820 .- 1469-8161. ; 136:1, s. 27-33
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Journal article (peer-reviewed)abstract
- Thioredoxin reductase (TrxR), a NADPH-dependent disulfide oxidoreductase, is vital in numerous cellular processes including defence against reactive oxygen species, cell proliferation and signal transduction. TrxRs occur in 2 forms, a high M-r enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low M-r form is present in bacteria, fungi, plants and some protozoan parasites. Our hypothesis is that the differences between the forms can be exploited in the development of selective inhibitors. In this study, cyclodextrin- and sulfonic acid-derived organotelluriums known to inhibit mammalian TrxR were investigated for their relative efficacy against P. falciparum TrxR (PfTrxR), a high M-r enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low M-r form of TrxR. The results suggest that selective inhibition of low M-r TrxRs is a feasible goal.
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| 3. |
- Thörn, Filip, 1992-, et al.
(author)
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Contemporary intergeneric hybridization and backcrossing among birds-of-paradise
- 2024
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In: Evolution Letters. - 2056-3744.
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Journal article (peer-reviewed)abstract
- Despite large differences in morphology, behavior and lek-mating strategies the birds-of-paradise are known to hybridize occasionally, even across different genera. Many of these bird-of-paradise hybrids were originally described as distinct species based on large morphological differences when compared to recognized species. Nowadays, these specimens are generally recognized as hybrids based on morphological assessments. Having fascinated naturalists for centuries, hybrid specimens of birds-of-paradise have been collected and the specimens kept in Natural History Collections. In the present study, we utilize this remarkable resource in a museomics framework and evaluate the genomic composition of most described intergeneric hybrids and some intrageneric hybrids. We show that the majority of investigated specimens are first-generation hybrids and that the parental species, in most cases, are in line with prior morphological assessments. We also identify two specimens that are the result of introgressive hybridization between different genera. Additionally, two specimens exhibit hybrid morphologies but have no identifiable signals of hybridization, which may indicate that minor levels of introgression can have large morphological effects. Our findings provide direct evidence of contemporary introgressive hybridization taking place between genera of birds-of-paradise in nature, despite markedly different morphologies and lek-mating behaviors.
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