A5010992334- Genomics and Chromatin Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Photosynthetic Processes and Mechanisms
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Advanced Electron Microscopy Techniques and Applications
- Metal-Catalyzed Oxygenation Mechanisms
- Particle accelerators and beam dynamics
- RNA Research and Splicing
- Cardiac electrophysiology and arrhythmias
- Biochemical and Molecular Research
- Algal biology and biofuel production
- Mechanisms of cancer metastasis
- Plant Genetic and Mutation Studies
- RNA Interference and Gene Delivery
High Energy Accelerator Research Organization
2016-2025
University of Tsukuba
2024-2025
Deleted Institution
2023
The Graduate University for Advanced Studies, SOKENDAI
2017-2021
Science Factory
2021
Institute of Materials Structure Science
2021
Japan Science and Technology Agency
2002-2018
Japan Biological Informatics Consortium
2008-2013
National Institute of Advanced Industrial Science and Technology
2011
The University of Tokyo
1990-2010
All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene1. This approach is fundamentally different the biosynthesis of short-chain (C10-C25) terpenes that formed polyisoprenyl diphosphates2-4. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate isopentenyl hexaprenyl as substrates,...
DNMT1 is an essential enzyme that maintains genomic DNA methylation, and its function regulated by mechanisms are not yet fully understood. Here, we report the cryo-EM structure of human bound to two natural activators: hemimethylated ubiquitinated histone H3. We find a hitherto unstudied linker, between RFTS CXXC domains, plays key role for activation. It contains conserved α-helix which engages crucial "Toggle" pocket, displacing previously described inhibitory allowing Recognition Helix...
The BET (bromodomains and extra terminal domain) family proteins recognize acetylated chromatin through their bromodomain act as transcriptional activators. One of the proteins, BRD2, associates with transcription factor E2F, mediator components CDK8 TRAP220, RNA polymerase II, well during mitosis. BRD2 contains two bromodomains (BD1 BD2), which are considered to be responsible for binding chromatin. protein specifically recognizes histone H4 tail at Lys12. Here, we report crystal structure...
Abstract C -Glycosides, in which a sugar moiety is linked via carbon-carbon (C-C) bond to non-sugar (aglycone), are found our food and medicine. The C-C cleaved by intestinal microbes the resulting aglycones exert various bioactivities. Although enzymes responsible for reactions have been identified, their catalytic mechanisms generality of nature remain be explored. Here, we present identification structural basis activation xenobiotic -glycosides heterocomplex -deglycosylation from soil...
Here we show a novel pathway of transcriptional regulation DNA-binding transcription factor by coupled interaction and modification (e.g., acetylation) through the domain (DBD). The oncogenic regulator SET was isolated affinity purification factors interacting with DBD cardiovascular KLF5. negatively regulated KLF5 DNA binding, transactivation, cell-proliferative activities. Down-regulation negative seen in response to KLF5-mediated gene activation. coactivator/acetylase p300, on other hand,...
Abstract Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent agonists, we develop a series TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography cryo-electron microscopy, identify the open conformation reveal...
Abstract Prasiola crispa , an aerial green alga, forms layered colonies under the severe terrestrial conditions of Antarctica. Since only far-red light is available at a deep layer colony, P. has evolved molecular system for photosystem II (PSII) excitation using with uphill energy transfer. However, basis underlying this remains elusive. Here, we purified light-harvesting chlorophyll (Chl)-binding protein complex from (Pc-frLHC) that excites PSII and revealed its ring-shaped structure...
P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. This mechanism particularly problematic cancer cells, where it diminishes the therapeutic efficacy of anticancer drugs. P-gp inhibitors, such as elacridar, have been developed circumvent decrease due An earlier study reported cryo-EM structure human P-gp-Fab (MRK-16) complex bound by two elacridar...
LysR‐type transcription regulators (LTTRs) comprise one of the largest families transcriptional in bacteria. They are typically homo‐tetrameric proteins and interact with promoter DNA ~ 50–60 bp. Earlier biochemical studies have suggested that LTTR binding to bends and, upon inducer binding, bend angle is reduced through a quaternary structure change tetrameric LTTR, leading activation transcription. To date, crystal structures full‐length LTTRs, DNA‐binding domains (DBD) their target DNAs,...
Abstract C-phycocyanin (CPC), a blue pigment protein, is an indispensable component of giant phycobilisomes, which are light-harvesting antenna complexes in cyanobacteria that transfer energy efficiently to photosystems I and II. X-ray crystallographic electron microscopy (EM) analyses have revealed the structure CPC be closed toroidal hexamer by assembling two trimers. In this study, structural characterization non-conventional octameric reported for first time. Analyses crystal cryogenic...
Giardia lamblia is a pathogenic unicellular eukaryotic parasite that causes giardiasis. Its genome encodes the canonical histones H2A, H2B, H3, and H4, which share low amino acid sequence identity with their human orthologues. We determined structure of G. nucleosome core particle (NCP) at 3.6 Å resolution by cryo-electron microscopy. form characteristic NCP, in visible 125 base-pair region DNA wrapped left-handed supercoil. The acidic patch on octamer deeper, due to an insertion extending...
A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally "Jampu Salo" was collected on Sulawesi Island, Indonesia. It identified Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) found for the first time Sulawesi; it previously reported only eastern Philippines Borneo. phytochemical study of S. led to isolation three unprecedented meroterpenoids, syzygioblanes A–C (1–3, respectively). These compounds might be biosynthesized through [4+2]...
LysR-type transcriptional regulators (LTTRs) are among the most abundant in bacteria. CbnR is an LTTR derived from Cupriavidus necator (formerly Alcaligenes eutrophus or Ralstonia eutropha) NH9 and involved activation of cbnABCD genes encoding chlorocatechol degradative enzymes. interacts with a cbnA promoter region approximately 60 bp length that contains recognition-binding site (RBS) activation-binding (ABS). Upon inducer binding, seems to undergo conformational changes, leading...
Nonribosomal peptide synthetases (NRPSs) are attractive targets for bioengineering to generate useful peptides. FmoA3 is a single modular NRPS composed of heterocyclization (Cy), adenylation (A), and peptidyl carrier protein (PCP) domains. It uses α-methyl-l-serine synthesize 4-methyloxazoline ring, probably with another Cy domain in the preceding module FmoA2. Here, we determined head-to-tail homodimeric structures by X-ray crystallography (apo-form, adenylyl-imidodiphosphate...
The steric zipper is a common hydrophobic packing structure of peptide side chains that forms between two adjacent β-sheet layers in amyloid and related fibrils. Although previous studies have revealed fragments derived from native protein sequences exhibit structures, their de novo designs rarely been studied. Herein, structures were artificially constructed the crystalline state by metal-induced folding assembly tetrapeptide Boc-3pa-X1-3pa-X2-OMe (3pa: β-(3-pyridyl)-l-alanine; X1 X2: amino...
Summary F o 1 -ATP synthase (F ) interconverts the energy of proton motive force ( pmf and that ATP via mechanical rotation rotor complex. The H + /ATP ratio, one most crucial parameters in bioenergetics, varies among species due to different number -binding c -subunits, resulting ratios ranging from 2.7 5. present study attempted enhance ratio significantly by employing a novel approach differs nature. We engineered form multiple peripheral stalks, each bound proton-conducting -subunit....
SbzP is a unique pyridoxal-5′-phosphate-dependent enzyme, which catalyses [3+2] annulation between the pyridinium ring of β-nicotinamide adenine dinucleotide (β-NAD) and an electron rich β,γ-unsaturated quinonoid derived from S-adenosylmethionine in natural product azaindane antibiotics biosynthesis. The SbzP-mediated has been proposed to be rare tandem C–C bond formation, but its structural basis catalytic mechanism remain largely unknown. Here we report β-NAD-complexed structure PseP (SbzP...
Abstract The heterochromatin protein HP1α consists of an N-terminal disordered tail (N-tail), chromodomain (CD), hinge region (HR), and C-terminal chromo shadow domain (CSD). While CD binds to the lysine9-trimethylated histone H3 (H3K9me3) in nucleosomes, CSD forms a dimer bridging two nucleosomes with H3K9me3. Phosphorylation serine residues N-tail enhances both H3K9me3 binding liquid–liquid phase separation (LLPS) by HP1α. We have used integrative structural methods, including nuclear...
3DED/MicroED (microED) is a method for obtaining electron diffraction data from cryogenic microscope (cryo-EM) under the liquid nitrogen temperature to reduce radiation damage. The capable of collecting individual crystals in field view microscope, even if several compounds are mixed. This was proposed by Gonen group US and Yonekura Japan 2013-2015 has attracted much attention researchers involved synthesis low-molecular-weight drug discovery. In this presentation, we first report on launch...
Carbohydrate-active enzymes are involved in the degradation, biosynthesis, and modification of carbohydrates vary with diversity carbohydrates. The glycoside hydrolase (GH) family 31 is one most diverse families carbohydrate-active enzymes, containing various that act on α-glycosides. However, function some GH31 groups remains unknown, as their enzymatic activity difficult to estimate due low amino acid sequence similarity between characterized uncharacterized members. Here, we performed a...
Nucleosomes around the promoter region are disassembled for transcription in response to various signals, such as acetylation and methylation of histones. Although interactions between histone-acetylation-recognizing bromodomains factors involved nucleosome disassembly have been reported, no structural basis connecting histone modifications has obtained. Here, we determined at 3.3 Å resolution crystal structure chaperone cell cycle gene 1 (CCG1) interacting factor A/antisilencing function...
Ribonuclease P (RNase P) is an endoribonuclease that catalyzes the processing of 5' leader sequence precursor tRNA (pre-tRNA). Ribonucleoprotein RNase and protein-only (PRORP) in eukaryotes have been extensively studied, but mechanism by which a prokaryotic nuclease recognizes cleaves pre-tRNA unclear. To gain insights into this mechanism, we studied homologs Aquifex (HARPs), thought to be enzymes approximately 23 kDa comprising only domain. We determined cryo-EM structure Aq880, first...
Protein nanocages are of increasing interest for use as drug capsules, but the encapsulation and release molecules at appropriate times require reversible association dissociation nanocages. One promising approach to addressing this challenge is design metal-dependent associating proteins. Such designed proteins typically have Cys or His residues protein surface connecting through metal-ion coordination. However, favor interactions with soft borderline metal ions, such Au+ Zn2+, classified...