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Mechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the in vitro kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of ?-secretase, an Alzheimer disease (AD)-associated IAP. mIAP variants with substitutions in active-site and putative substrate-gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His?Thr). The aromatic ring, but not the hydroxyl substituent, within Tyr of the catalytic Tyr?Asp (YD) motif plays a catalytic role, and the hydrolysis reaction incorporates bulk water as in soluble aspartyl proteases. mIAP hydrolyzes the transmembrane region of C100 at two major presenilin cleav ...

Cytochrome c oxidase (COX) was initially purified more than 70 years ago. A tremendous amount of insight into its structure and function has since been gleaned from biochemical, biophysical, genetic, and molecular studies. As a result, we now appreciate that COX relies on its redox-active metal centers (heme a and a3, CuA and CuB) to reduce oxygen and pump protons in a reaction essential for most eukaryotic life. Questions persist, however, about how individual structural subunits are assembled into a functional holoenzyme. Here, we focus on what is known and what remains to be learned about the accessory proteins that facilitate CuA site maturation.

The copper-containing superoxide dismutases (SODs) represent a large family of enzymes that participate in the metabolism of reactive oxygen species by disproportionating superoxide anion radical to oxygen and hydrogen peroxide. Catalysis is driven by the redox-active copper ion, and in most cases, SODs also harbor a zinc at the active site that enhances copper catalysis and stabilizes the protein. Such bimetallic Cu,Zn-SODs are widespread, from the periplasm of bacteria to virtually every organelle in the human cell. However, a new class of copper-containing SODs has recently emerged that function without zinc. These copper-only enzymes serve as extracellular SODs in specific bacteria (i.e. Mycobacteria), throughout the fungal kingdom, and in the fungus-like oomycetes. The eukaryotic copper-only SODs are particularly unique in that they lack an electrostatic loop for substrate guidance and have an unusual open-access copper site, yet they can still react with superoxide at rates limit ...

Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition-metal signaling, where dynamic changes in transitional metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition-metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

Copper is essential for most organisms as a cofactor for key enzymes involved in fundamental processes such as respiration and photosynthesis. However, copper also has toxic effects in cells, which is why eukaryotes and prokaryotes have evolved mechanisms for safe copper handling. A new family of bacterial proteins uses a Cys-rich four-helix bundle to safely store large quantities of Cu(I). The work leading to the discovery of these proteins, their properties and physiological functions, and how their presence potentially impacts the current views of bacterial copper handling and use are discussed in this review.

Methanobactins (Mbns) are ribosomally produced, post-translationally modified natural products that bind copper with high affinity and specificity. Originally identified in methanotrophic bacteria, which have a high need for copper, operons encoding these compounds have also been found in many non-methanotrophic bacteria. The proteins responsible for Mbn biosynthesis include several novel enzymes. Mbn transport involves export through a multidrug efflux pump and re-internalization via a TonB-dependent transporter. Release of copper from Mbn and the molecular basis for copper regulation of Mbn production remain to be elucidated. Future work is likely to result in the identification of new enzymatic chemistry, opportunities for bioengineering and drug targeting of copper metabolism, and an expanded understanding of microbial metal homeostasis.

This 11th Thematic Metals in Biology Thematic Series deals with copper, a transition metal with a prominent role in biochemistry. Copper is a very versatile element, and both deficiencies and excesses can be problematic. The five Minireviews in this series deal with several aspects of copper homeostasis in microorganisms and mammals and the role of this metal in two enzymes, copper-only superoxide dismutase and cytochrome c oxidase.

Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk as does pITAM. However, it is unknown whether integrins and pITAM use the same mechanism to activate Syk. Here, using purified Syk protein and fluorescence-based enzyme assay we investigated whether interaction of the integrin ?3 cytoplasmic domain with the Syk regulatory domain causes changes in Syk ...

2018年3月30日、国立国会図書館（NDL）は、「国立国会図書館書誌データ作成・提供計画2018-2020」を策定して公開しました。 この計画は「国立国会図書館の書誌データ作成・提供の新展開（2013）」の後継となる計画で、2018年度からの3年間を計画期間とし、NDLの書誌データ提供の強化と、そのための書誌データ作成の基盤整備を具体的かつ着実に進めることを目的としています。「書誌データ提供の強化」として、新しい日本目録規則への対応、典拠コントロールの拡大、雑誌記事索引の拡充、新しい書誌フレームワークの国際動向の把握、全国書誌を中心とした書誌データの利活用促進の5点、「書誌データ作成の基盤整備」として、職員の能力向上、外部資源の活用とシステム機能の強化等の2点が挙げられています。 書誌データの作成およ ...

この動画は平成２９年８月２２日～２３日に開催された福島県主催のモニターツアー「ふくしまの食の安全を知る旅」で、タレントの向井亜紀さんをツアーリーダー兼レポーターに迎え、生産者さんとの交流等を通して感じた、福島県への「共感」や「食の安全」について目で見て体験したレポートを参加者でもある女子美術大学の学生さん達が動画として編集をしてくれました。 首都圏消費者等交流事業（モニターツアー）とは？ 「食と放射能」や福島県の県産品に対する正しい知識を得て、理解をしていただくために、首都圏の消費者を対象にモニターツアーを開催しています。 平成２５～２９年度で４０回モニターツアーを開催し、延べ１０００名を超える消費者の皆さんに参加いただきました。（向井亜紀さんがツアーリーダーと ...