Suntory Institute for Bioorganic Research

Osaka, Japan

Suntory Institute for Bioorganic Research

Osaka, Japan
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Shimamoto K.,Suntory Institute for Bioorganic Research
Bulletin of the Chemical Society of Japan | Year: 2016

Membrane proteins, such as receptors, transporters, and enzymes, play various roles in the survival of organisms. Discovery and development of new bioactive molecules interacting with these proteins are indispensable for understanding the mechanisms of biological events. This account summarizes our efforts on (1) design and synthesis of glutamate transporter blockers to elucidate the mechanism of excitatory neurotransmission process and (2) identification of a novel glycolipid that is essential for membrane protein integration. © 2016 The Chemical Society of Japan.

Minakata H.,Suntory Institute for Bioorganic Research
Annals of the New York Academy of Sciences | Year: 2010

Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals. © 2010 New York Academy of Sciences.

Takahashi T.,Suntory Institute for Bioorganic Research | Hamaue N.,Health Sciences University of Hokkaido
FEBS Letters | Year: 2010

A full-length cDNA encoding an acetylcholinesterase (AChE) from Hydra magnipapillata was isolated. All of the important aromatic residues that line a catalytic gorge in cholinesterases of other species were conserved, but the sequences of peripheral anionic and choline binding sites were not. Hydra AChE, expressed in Xenopus oocytes, showed AChE activity. The gene was expressed in both ectodermal and endodermal epithelial cells except for the tentacles and basal disk. AChE gene expression was not detected in the regenerating tips in either the head or the foot, indicating that regeneration is controlled by the non-neuronal cholinergic system in Hydra. © 2009 Federation of European Biochemical Societies.

Sugase K.,Suntory Institute for Bioorganic Research
Journal of Biomolecular NMR | Year: 2011

We developed a new method to elucidate the binding kinetics kon and koff, and the dissociation constant KD (=k off/kon), of protein-protein interactions without observable bound resonances of the protein of interest due to high molecular weight in a complex with a large target protein. In our method, kon and koff rates are calculated from the analysis of longitudinal relaxation rates of free resonances measured for multiple samples containing different concentration ratios of 15N-labeled protein and substoichiometric amounts of the target protein. The method is applicable to interactions that cannot be analyzed by relaxation dispersion spectroscopy due to slow interactions on millisecond to second timescale and/or minimal conformational (chemical shift) change upon binding. We applied the method to binding of the B1 domain of protein G (GB1) to immunoglobulin G, and derived the binding kinetics despite the absence of observable bound GB1 resonances. © 2011 Springer Science+Business Media B.V.

Araki R.,Suntory Institute for Bioorganic Research | Murata J.,Suntory Institute for Bioorganic Research | Murata Y.,Suntory Institute for Bioorganic Research
Plant and Cell Physiology | Year: 2011

Recent advances in our understanding of how graminaceous plants take up insoluble forms of iron from the rhizosphere and mobilize them in plant tissues are primarily based on the identification of various transporters that are specific to metal-phytosiderophore (PS) complexes containing mugineic acid and deoxymugineic acid. Barley (Hordeum vulgare L.) yellow stripe 1 (HvYS1) is a metal-PS transporter that preferentially transports Fe(III)-PS compared with other metal complexes. Here, we report the cloning and characterization of HvYSL2, a novel metal-PS transporter encoding gene. HvYSL2 is composed of 702 amino acids with 14 transmembrane domains, which are conserved among this class of transporters, and exhibits 67.3 identity to HvYS1. Electrophysiological experiments with Xenopus laevis oocytes revealed that HvYSL2 transports PS complexes with Fe(III), Zn(II), Ni(II), Cu(II), Mn(II) or Co(II); this constitutes a broader range of substrate preference than HvYS1. Real-time PCR analysis revealed that HvYSL2 mRNA is expressed in shoots and also in roots, where it is induced under iron-deficient conditions. Moreover, immunohistochemistry in roots revealed that HvYSL2 is localized to the endodermis, whereas HvYS1 is expressed primarily in the epidermis. These data suggest that HvYSL2 is spatially distinct from HvYS1 and plays a unique role in delivering a broad range of essential metals in barley. © 2011 The Author.

Satake H.,Suntory Institute for Bioorganic Research | Sekiguchi T.,Suntory Institute for Bioorganic Research
Frontiers in Immunology | Year: 2012

Defensive systems against pathogens are responsible not only for survival or lifetime of an individual but also for the evolution of a species. Innate immunity is expected to be more important for invertebrates than mammals, given that adaptive immunity has not been acquired in the former. Toll-like receptors (TLRs) have been shown to play a crucial role in host defense of pathogenic microbes in innate immunity of mammals. Recent genome-wide analyses have suggested that TLR or their related genes are conserved in invertebrates. In particular, numerous TLR-related gene candidates were detected in deuterostome invertebrates, including a sea urchin (222 TLR-related gene candidates) and amphioxus (72TLR-related gene candidates). Molecular phylogenetic analysis verified that most of sea urchin or amphioxus TLR candidates are paralogous, suggesting that these organisms expanded TLR-related genes in a species-specific manner. In contrast, another deuterostome invertebrate, the ascidian Ciona intestinalis, was found to possess only two TLR genes. Moreover, Ciona TLRs, Ci-TLR1 and Ci-TLR2, were shown to possess "hybrid" functionality of mammalian TLRs. Such functionality of Ci-TLRs could not be predicted by sequence comparison with vertebrate TLRs, indicating confounding evolutionary lineages of deuterostome invertebrate TLRs or their candidates. In this review article, we present recent advances in studies ofTLRs or their candidates among deuterostome invertebrates, and provide insight into an evolutionary process of TLRs. © 2012 Satake and Sekiguchi.

Chung W.J.,Nanyang Technological University | Heddi B.,Nanyang Technological University | Tera M.,Tokyo University of Agriculture and Technology | Tera M.,Suntory Institute for Bioorganic Research | And 3 more authors.
Journal of the American Chemical Society | Year: 2013

Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through π-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs. © 2013 American Chemical Society.

Takahashi T.,Suntory Institute for Bioorganic Research
Protein and Peptide Letters | Year: 2013

Peptides are known to play important developmental and physiological roles in signaling. The rich diversity of peptides, with functions as diverse as intercellular communication, neurotransmission and signaling that spatially and temporally controls axis formation and cell differentiation, hints at the wealth of information passed between interacting cells. Little is known about peptides that control developmental processes such as cell differentiation and pattern formation in metazoans. The cnidarian Hydra is one of the most basic metazoans and is a key model system for study of the peptides involved in these processes. We developed a novel peptidomic approach for the isolation and identification of functional peptide signaling molecules from Hydra (the Hydra Peptide Project). Over the course of this project, a wide variety of novel neuropeptides were identified. Most of these peptides act directly on muscle cells and their functions include induction of contraction and relaxation. Some peptides are involved in cell differentiation and morphogenesis. Moreover, epitheliopeptides that are produced by epithelial cells were originally identified in Hydra. Some of these epitheliopeptides exhibit morphogen-like activities, whereas others are involved in regulating neuron differentiation, possibly through neuron-epithelial cell interactions. We also describe below our high-throughput reverse-phase nano-flow LCMALDI-TOF-MS/MS approach, which has proved a powerful tool for the discovery of novel peptide signaling molecules in Hydra. © 2013 Bentham Science Publishers.

Satake H.,Suntory Institute for Bioorganic Research | Ono E.,Suntory Business Expert Ltd. | Murata J.,Suntory Institute for Bioorganic Research
Journal of Agricultural and Food Chemistry | Year: 2013

Plant physiological, epidemiological, and food science studies have shed light on lignans as healthy diets for the reduction of the risk of lifestyle-related noncommunicable diseases and, thus, the demand for lignans has been rapidly increasing. However, the low efficiency and instability of lignan production via extraction from plant resources remain to be resolved, indicating the requirement for the development of new procedures for lignan production. The metabolic engineering of lignan-biosynthesizing plants is expected to be most promising for efficient, sustainable, and stable lignan production. This is supported by the recent verification of biosynthetic pathways of major dietary lignans and the exploration of lignan production via metabolic engineering using transiently gene-transfected or transgenic plants. The aim of this review is to present an overview of the biosynthetic pathways, biological activities, and metabolic engineering of lignans and also perspectives in metabolic engineering-based lignan production using transgenic plants for practical application. © 2013 American Chemical Society.

Koyama T.,Suntory Institute for Bioorganic Research
Frontiers in Plant Science | Year: 2014

Leaf senescence is the last stage of leaf development and is accompanied by cell death. In contrast to senescence in individual organisms that leads to death, leaf senescence is associated with dynamic processes that include the translocation of nutrients from old leaves to newly developing or storage tissues within the same plant. The onset of leaf senescence is largely regulated by age and internal and external stimuli, which include the plant hormone ethylene. Earlier studies have documented the important role of ethylene in the regulation of leaf senescence. The production of ethylene coincides with the onset of leaf senescence, whereas the application of ethylene to plants induces precocious leaf senescence. Recently, many studies have described the components of ethylene signaling and biosynthetic pathways that are involved in modulating the onset of leaf senescence. Particularly, transcription factors (TFs) integrate ethylene signals with those from environmental and developmental factors to accelerate or delay leaf senescence. This review aims to discuss the regulatory cascade involving ethylene andTFs in the regulation of onset of leaf senescence. © 2014 Koyama.

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