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Nitrogenase is the enzyme that reduces atmospheric dinitrogen (N2) to ammonia (NH3) in biological systems. It catalyzes a series of single-electron transfers from the donor iron protein (Fe protein) to the molybdenum?iron protein (MoFe protein) that contains the iron?molybdenum cofactor (FeMo-co) sites where N2 is reduced to NH3. The P-cluster in the MoFe protein functions in nitrogenase catalysis as an intermediate electron carrier between the external electron donor, the Fe protein, and the FeMo-co sites of the MoFe protein. Previous work has revealed that the P-cluster undergoes redox-dependent structural changes and that the transition from the all-ferrous resting (PN) state to the two-electron oxidized P2+ state is accompanied by protein serine hydroxyl and backbone amide ligation to iron. In this work, the MoFe protein was poised at defined potentials with redox mediators in an electrochemical cell, and the three distinct structural states of the P-cluster (P2+, P1+, and PN) were ...

Human ?-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of the allergic inflammatory responses in asthma. During acute hypersensitivity reactions, mast cells degranulate, releasing active tetramer as a complex with proteoglycans. Extensive efforts have focused on developing therapeutic ?-tryptase inhibitors, but its unique activation mechanism is less well-explored. Tryptase is active only after proteolytic removal of the pro-domain followed by tetramer formation via two distinct symmetry-related interfaces. We show that the cleaved I16G mutant cannot tetramerize, likely due to impaired insertion of its N terminus into its ?activation pocket,? indicating allosteric linkage at multiple sites on each protomer. We engineered cysteines into each of the two distinct interfaces (Y75C for small or I99C for large) to assess the activity of each tetramer and disulfide-locked dimer. Using size-exclusion chromatography and enzymatic assays, we demonstrate that the tw ...

The pyruvate dehydrogenase complex (PDC) is a key control point of energy metabolism and is subject to regulation by multiple mechanisms, including posttranslational phosphorylation by pyruvate dehydrogenase kinase (PDK). Pharmacological modulation of PDC activity could provide a new treatment for diabetic cardiomyopathy, as dysregulated substrate selection is concomitant with decreased heart function. Dichloroacetate (DCA), a classic PDK inhibitor, has been used to treat diabetic cardiomyopathy, but the lack of specificity and side effects of DCA indicate a more specific inhibitor of PDK is needed. This study was designed to determine the effects of a novel and highly selective PDK inhibitor, 2((2,4-dihydroxyphenyl)sulfonyl) isoindoline-4,6-diol (designated PS10), on pyruvate oxidation in diet-induced obese (DIO) mouse hearts compared with DCA-treated hearts. Four groups of mice were studied: lean control, DIO, DIO + DCA, and DIO + PS10. Both DCA and PS10 improved glucose tolerance in ...

The kynurenine pathway is the primary route for l-tryptophan degradation in mammals. Intermediates and side products of this pathway are involved in immune response and neurodegenerative diseases. This makes the study of enzymes, especially those from mammalian sources, of the kynurenine pathway worthwhile. Recent studies on a bacterial version of an enzyme of this pathway, 2-aminomuconate semialdehyde (2-AMS) dehydrogenase (AMSDH), have provided a detailed understanding of the catalytic mechanism and identified residues conserved for muconate semialdehyde recognition and activation. Findings from the bacterial enzyme have prompted the reconsideration of the function of a previously identified human aldehyde dehydrogenase, ALDH8A1 (or ALDH12), which was annotated as a retinal dehydrogenase based on its ability to preferentially oxidize 9-cis-retinal over trans-retinal. Here, we provide compelling bioinformatics and experimental evidence that human ALDH8A1 should be reassigned to the mi ...

Many mutations in genes encoding proteins such as Parkin, PTEN-induced putative kinase 1 (PINK1), protein deglycase DJ-1 (DJ-1 or PARK7), leucine-rich repeat kinase 2 (LRRK2), and ?-synuclein have been linked to familial forms of Parkinson's disease (PD). The consequences of these mutations, such as altered mitochondrial function and pathological protein aggregation, are starting to be better understood. However, little is known about the mechanisms explaining why alterations in such diverse cellular processes lead to the selective loss of dopamine (DA) neurons in the substantia nigra (SNc) in the brain of individuals with PD. Recent work has shown that one of the reasons for the high vulnerability of SNc DA neurons is their high basal rate of mitochondrial oxidative phosphorylation (OXPHOS), resulting from their highly complex axonal arborization. Here, we examined whether axonal growth and basal mitochondrial function are altered in SNc DA neurons from Parkin-, Pink1-, or DJ-1?KO mic ...

Clear cell renal cell carcinoma (ccRCC) represents the most common kidney cancer worldwide. Increased cell proliferation associated with abnormal microRNA (miRNA) regulation are hallmarks of carcinogenesis. Ankyrin repeat and single KH domain 1 (ANKHD1) is a highly conserved protein found to interact with core cancer pathways in Drosophila; however, its involvement in RCC is completely unexplored. Quantitative PCR studies coupled with large-scale genomics data sets demonstrated that ANKHD1 is significantly up-regulated in kidneys of RCC patients when compared with healthy controls. Cell cycle analysis revealed that ANKHD1 is an essential factor for RCC cell division. To understand the molecular mechanism(s) utilized by ANKHD1 to drive proliferation, we performed bioinformatics analyses that revealed that ANKHD1 contains a putative miRNA-binding motif. We screened 48 miRNAs with tumor-enhancing or -suppressing activities and found that ANKHD1 binds to and regulates three tumor-suppressi ...

Major histocompatibility complex-I??2m dimers (MHC-I) bind peptides derived from intracellular proteins, enabling the immune system to distinguish between normal cells and those expressing pathogen-derived or mutant proteins. The peptides bind to MHC-I in the endoplasmic reticulum (ER), and this binding is facilitated by the peptide loading complex (PLC), which contains calreticulin (CRT). CRT associates with MHC-I via a conserved glycan present on MHC-I and recruits it to the PLC for peptide binding. Somatic frameshift mutations in CRT (CRT-FS) drive the proliferation of a subset of myeloproliferative neoplasms, which are chronic blood tumors. All CRT-FS proteins have a C-terminal sequence lacking the normal ER-retention signal and possessing a net negative charge rather than the normal positive charge. We characterized the effect of CRT-FS on antigen presentation by MHC-I in human cells. Our results indicate that CRT-FS cannot mediate CRT's peptide loading function in the PLC. Cells ...

2018年6月22日、文部科学省が、「教育委員会等における小学校プログラミング教育に関する取組状況等について」（平成29年度）を公表しました。 同省が、委託事業として、教育委員会の担当者を対象に、2020年度のプログラミング教育の全面実施に向けた取組状況等について尋ねたアンケート調査の報告書で、同省が3月30日に「小学校プログラミング教育の手引（第一版）」を公表する以前の時点での取組状況がまとめられています。 新着情報（文部科学省） http://www.mext.go.jp/b_menu/news/index.html ※平成30年06月22日欄に「教育委員会等における小学校プログラミング教育に関する取組状況等」とあります。 教育委員会等における小学校プログラミング教育に関する取組状況等（文部科学省） http://www.mext.go.jp/a_menu/shotou/zyouhou/detail/1406307.htm 続きを ...

6月22日（金）に幼児教育学科の2年生は、「生活と環境」の授業の一環で62年館の屋上に野菜やハーブの苗を植えました。当日は、JAふくしまさくらの皆さんにご指導を頂きました。本学の屋上緑化活動は8年ぶりになりますが、美味しい野菜やハーブがたくさん収穫できるとよいですね。収穫した野菜とハーブは、本学の学生食堂の献立にも利用する予定です。

話題を読む キーワードは「沖縄・琉球」について