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71.
Olga P. Nyssen Angeles Perez‐Aisa Luis Rodrigo Manuel Castro Pilar Mata Romero Juan Ortuo Jesus Barrio Jose Maria Huguet Ines Modollel Noelia Alcaide Alfredo Lucendo Xavier Calvet Monica Perona Barbara Gomez Blas Jose Gomez Rodriguez Pilar Varela Manuel Jimenez‐Moreno Manuel Dominguez‐Cajal Liliana Pozzati Diego Burgos Luis Bujanda Jenifer Hinojosa Javier Molina‐Infante Tommaso Di Maira Luis Ferrer Luis Fernndez‐Salazar Ariadna Figuerola Llucia Tito Cristobal de la Coba Judith Gomez‐Camarero Nuria Fernandez Maria Caldas Ana Garre Elena Resina Ignasi Puig Colm OMorain Francis Megraud Javier P. Gisbert 《Helicobacter》2020,25(5)
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Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus. 下载免费PDF全文
Q Tu L H Pinto G Luo M A Shaughnessy D Mullaney S Kurtz M Krystal R A Lamb 《Journal of virology》1996,70(7):4246-4252
The influenza A virus M2 integral membrane protein has ion channel activity that can be inhibited by the antiviral drug amantadine. Recently, a spirene-containing compound, BL-1743 (2-[3-azaspiro (5,5)undecanol]-2-imidazoline), that inhibits influenza virus growth was identified (S. Kurtz, G. Lao, K. M. Hahnenberger, C. Brooks, O. Gecha, K. Ingalls, K.-I. Numata, and M. Krystal, Antimicrob. Agents Chemother. 39:2204-2209, 1995). We have examined the ability of BL-1743 to inhibit the M2 ion channel when expressed in oocytes of Xenopus laevis. BL-1743 inhibition is complete as far as can be measured by electrophysiological methods and is reversible, with a reverse reaction rate constant of 4.0 x 10(-3) s(-1). In contrast, amantadine inhibition is irreversible within the time frame of the experiment. However, BL-1743 inhibition and amantadine inhibition have similar properties. The majority of isolated influenza viruses resistant to BL-1743 are also amantadine resistant. In addition, all known amino acid changes which result in amantadine resistance also confer BL-1743 resistance. However, one BL-1743-resistant virus isolated, designated M2-I35T, contained the change Ile-35-->Thr. This virus is >70-fold more resistant to BL-1743 and only 10-fold more resistant to amantadine than the wild-type virus. When the ion channel activity of M2-I35T was examined in oocytes, it was found that M2-I35T is BL-1743 resistant but is reversibly inhibited by amantadine. These findings suggest that these two drugs interact differently with the M2 protein transmembrane pore region. 相似文献
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Selena G. Burgess Isabel Peset Nimesh Joseph Tommaso Cavazza Isabelle Vernos Mark Pfuhl Fanni Gergely Richard Bayliss 《PLoS genetics》2015,11(7)
The essential mammalian gene TACC3 is frequently mutated and amplified in cancers and its fusion products exhibit oncogenic activity in glioblastomas. TACC3 functions in mitotic spindle assembly and chromosome segregation. In particular, phosphorylation on S558 by the mitotic kinase, Aurora-A, promotes spindle recruitment of TACC3 and triggers the formation of a complex with ch-TOG-clathrin that crosslinks and stabilises kinetochore microtubules. Here we map the Aurora-A-binding interface in TACC3 and show that TACC3 potently activates Aurora-A through a domain centered on F525. Vertebrate cells carrying homozygous F525A mutation in the endogenous TACC3 loci exhibit defects in TACC3 function, namely perturbed localization, reduced phosphorylation and weakened interaction with clathrin. The most striking feature of the F525A cells however is a marked shortening of mitosis, at least in part due to rapid spindle assembly. F525A cells do not exhibit chromosome missegregation, indicating that they undergo fast yet apparently faithful mitosis. By contrast, mutating the phosphorylation site S558 to alanine in TACC3 causes aneuploidy without a significant change in mitotic duration. Our work has therefore defined a regulatory role for the Aurora-A-TACC3 interaction beyond the act of phosphorylation at S558. We propose that the regulatory relationship between Aurora-A and TACC3 enables the transition from the microtubule-polymerase activity of TACC3-ch-TOG to the microtubule-crosslinking activity of TACC3-ch-TOG-clathrin complexes as mitosis progresses. Aurora-A-dependent control of TACC3 could determine the balance between these activities, thereby influencing not only spindle length and stability but also the speed of spindle formation with vital consequences for chromosome alignment and segregation. 相似文献
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Birch Quinn T. Potter Phillip M. Pinto Patricio X. Dionysiou Dionysios D. Al-Abed Souhail R. 《Reviews in Environmental Science and Biotechnology》2020,19(2):275-336
Reviews in Environmental Science and Bio/Technology - The growing and pervasive presence of plastic pollution has attracted considerable interest in recent years, especially small... 相似文献
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Cassilda Pereira Inês S. Rodrigues Liliana M.G. Pereira Johnny Lisboa Rute D. Pinto Leonor Araújo Pedro Oliveira Roland Benz Nuno M.S. dos Santos Ana do Vale 《Cellular microbiology》2020,22(1)
Apoptosis‐inducing protein of 56 kDa (AIP56) is a major virulence factor of Photobacterium damselae subsp. piscicida, a gram‐negative pathogen that infects warm water fish species worldwide and causes serious economic losses in aquacultures. AIP56 is a single‐chain AB toxin composed by two domains connected by an unstructured linker peptide flanked by two cysteine residues that form a disulphide bond. The A domain comprises a zinc‐metalloprotease moiety that cleaves the NF‐kB p65, and the B domain is involved in binding and internalisation of the toxin into susceptible cells. Previous experiments suggested that disruption of AIP56 disulphide bond partially compromised toxicity, but conclusive evidences supporting the importance of that bond in intoxication were lacking. Here, we show that although the disulphide bond of AIP56 is dispensable for receptor recognition, endocytosis, and membrane interaction, it needs to be intact for efficient translocation of the toxin into the cytosol. We also show that the host cell thioredoxin reductase‐thioredoxin system is involved in AIP56 intoxication by reducing the disulphide bond of the toxin at the cytosol. The present study contributes to a better understanding of the molecular mechanisms operating during AIP56 intoxication and reveals common features shared with other AB toxins. 相似文献