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101.
102.
103.
Balasubramanian Chandramouli Sara Del Galdo Giordano Mancini Vincenzo Barone 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(2):472-480
Background
The mechanism of how the hydrophilic threefold channel (C3) of ferritin nanocages facilitates diffusion of diverse metal ions into the internal cavity remains poorly explored.Methods
Computational modeling and free energy estimations were carried out on R. catesbeiana H´ ferritin. Transit features and associated energetics for Fe2+, Mg2+, Zn2+ ions through the C3 channel have been examined.Results
We highlight that iron conduction requires the involvement of two Fe2+ ions in the channel. In such doubly occupied configuration, as observed in X-ray structures, Fe2+ is displaced from the internal site (stabilized by D127) at lower energetic cost. Moreover, comparison of Fe2+, Mg2+ and Zn2+ transit features shows that E130 geometric constriction provides not only an electrostatic anchor to the incoming ions but also differentially influence their diffusion kinetics.Conclusions
Overall, the study provides insights into Fe2+ entry mechanism and characteristic features of metal-protein interactions that influence the metal ions passage. The dynamics data suggest that E130 may act as a metal selectivity gate. This implicates an ion-specific entry mechanism through the channel with the distinct diffusion kinetics being the discriminating factor.General Significance
Ferritin nanocages not only act as biological iron reservoirs but also have gained importance in material science as template scaffolds for synthesizing metal nanoparticles. This study provides mechanistic understanding on the conduction of different metal ions through the channel. 相似文献104.
105.
The aim of this study was to carry out a comparison of the ability to discriminate between extreme chronotypes, i.e., morning- and evening-types, among the Morningness-Eveningness Questionnaire (MEQ) and its reduced version (rMEQ). To this end a secondary analysis of cohort studies, using two different approaches, was carried out. The first, subjective, relied on the computing of overlap between extreme chronotypes according to their hourly ideal bedtime, get-up time and midpoint of sleep reported at the MEQ and rMEQ, while the second, objective, on the corresponding actual-actigraphic times. At the subjective approach, 2706 participants filled in the MEQ, while 940 the rMEQ (age range of both groups: 18–30 years). The overlap was significantly lower among those who filled the rMEQ than MEQ when considering ideal midpoint of sleep (13.70% and 46.28%, respectively) and get-up time (47.04% and 62.34%, respectively). At the objective approach, 51 participants filled in the MEQ while 52 the rMEQ (age range: 19–30 years in both groups) at the end of one week of actigraphic recording. No significantly different overlap across those who filled the MEQ or rMEQ was observed with reference to the examined actigraphic times. Results of subjective assessment showed as rMEQ more clearly discriminated between extreme chronotypes than MEQ. The attempt to find an objective confirmation did not provide the same results, probably as a consequence of a masking effect by social rhythms. 相似文献
106.
Paola Irato Alessandro Santon Elena Ossi Vincenzo Albergoni 《The Histochemical journal》2001,33(2):79-86
The interactions between two essential metals, Cu and Zn, and the localization and concentration of metallothionein have been studied in rat liver and kidney. Rats receiving daily intraperitoneal injections of Cu for 3 days, or Zn for 2 days, or Cu for 3 days followed by Zn for 2 days, were sacrificed 24, 72, 120h after the final injection. Our data indicate that Cu and Zn are both good inductors of metallothionein synthesis in rat tissues. Synergism between Cu and Zn in metallothionein synthesis was also observed as indicated by immunocytochemical experiments and chemical analysis. Moreover, in rats injected with Cu followed by Zn, the localization of metallothionein and the concentrations of both metallothionein and metal differed over time according to the organs considered. In rat kidney, a delay in the excretory process was also observed and metallothionein was present 120h after the last injection. 相似文献
107.
Villani GR Balzano N Vitale D Saviano M Pavone V Di Natale P 《Biochimica et biophysica acta》1999,1453(2):185-192
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ASB). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation. 相似文献
108.
Stereospecific synthesis of "para-hydroxymexiletine" and sodium channel blocking activity evaluation
Catalano A Carocci A Fracchiolla G Franchini C Lentini G Tortorella V De Luca A De Bellis M Desaphy JF Conte Camerino D 《Chirality》2004,16(2):72-78
Both enantiomers of "para-hydroxymexiletine" (PHM), one of the main metabolites of mexiletine, were synthesized and fully characterized. Properties of (R)- and (S)-PHM, in terms of blocking potency and stereoselectivity on frog skeletal muscle Na(+) channels, were evaluated. The presence of a hydroxy group on the aryloxy moiety in the 4-position, as in PHM, reduced potency with respect to mexiletine in reducing I(Na max). However, PHM showed clear use-dependent behavior similar to that of mexiletine and, in contrast with what is observed with the parent compound, maintained its stereoselectivity during the use-dependent block. Chirality 16:72-78, 2004. 相似文献
109.
Sharan SK Pyle A Coppola V Babus J Swaminathan S Benedict J Swing D Martin BK Tessarollo L Evans JP Flaws JA Handel MA 《Development (Cambridge, England)》2004,131(1):131-142
The role of Brca2 in gametogenesis has been obscure because of embryonic lethality of the knockout mice. We generated Brca2-null mice carrying a human BAC with the BRCA2 gene. This construct rescues embryonic lethality and the mice develop normally. However, there is poor expression of the transgene in the gonads and the mice are infertile, allowing examination of the function of BRCA2 in gametogenesis. BRCA2-deficient spermatocytes fail to progress beyond the early prophase I stage of meiosis. Observations on localization of recombination-related and spermatogenic-related proteins suggest that the spermatocytes undergo early steps of recombination (DNA double strand break formation), but fail to complete recombination or initiate spermiogenic development. In contrast to the early meiotic prophase arrest of spermatocytes, some mutant oocytes can progress through meiotic prophase I, albeit with a high frequency of nuclear abnormalities, and can be fertilized and produce embryos. Nonetheless, there is marked depletion of germ cells in adult females. These studies provide evidence for key roles of the BRCA2 protein in mammalian gametogenesis and meiotic success. 相似文献
110.
Manna C Migliardi V Golino P Scognamiglio A Galletti P Chiariello M Zappia V 《The Journal of nutritional biochemistry》2004,15(8):461-466
The potential protective effects of oleuropein, a dietary antioxidant of olive oil, has been investigated in the isolated rat heart. The organs were subjected to 30 minutes of no-flow global ischemia and then reperfused. At different time intervals, the coronary effluent was collected and assayed for creatine kinase activity as well as for reduced and oxidized glutathione. In addition, the extent of lipid peroxidation was evaluated by measuring thiobarbituric acid reactive substance concentration in cardiac muscle. Pretreatment with 20 microg/g oleuropein before ischemia resulted in a significant decrease in creatine kinase and reduced glutathione release in the perfusate. The protective effect of oleuropein against the post-ischemic oxidative burst was investigated by measuring the release, in the coronary effluent, of oxidized glutathione, a sensitive marker of heart's exposure to oxidative stress. Reflow in ischemic hearts was accompanied by a prompt release of oxidized glutathione; in ischemic hearts pretreated with oleuropein, this release was significantly reduced. Membrane lipid peroxidation was also prevented by oleuropein. The reported data provide the first experimental evidence of a direct cardioprotective effect of oleuropein in the acute events that follow coronary occlusion, likely because of its antioxidant properties. This finding strengthens the hypothesis that the nutritional benefit of olive oil in the prevention of coronary heart disease can be also related to the high content of oleuropein and its derivatives. Moreover, our data, together with the well documented antithrombotic and antiatherogenic activity of olive oil polyphenols, indicate these antioxidants as possible therapeutic tools for the pharmacological treatment of coronary heart disease as well as in the case of cardiac surgery, including transplantation. 相似文献