A5014200624- Enzyme Structure and Function
- Metal-Catalyzed Oxygenation Mechanisms
- Amino Acid Enzymes and Metabolism
- Photosynthetic Processes and Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Microbial metabolism and enzyme function
- Cancer, Hypoxia, and Metabolism
- Porphyrin Metabolism and Disorders
- Microbial bioremediation and biosurfactants
- Biochemical and Molecular Research
- Biochemical effects in animals
- Medical Imaging Techniques and Applications
- Microbial Metabolic Engineering and Bioproduction
- Metalloenzymes and iron-sulfur proteins
- Galectins and Cancer Biology
- DNA and Nucleic Acid Chemistry
- Hemoglobin structure and function
- Protein Tyrosine Phosphatases
- Mass Spectrometry Techniques and Applications
- Porphyrin and Phthalocyanine Chemistry
- Microbial Natural Products and Biosynthesis
- Glutathione Transferases and Polymorphisms
- Nanoplatforms for cancer theranostics
High Energy Accelerator Research Organization
2016-2025
Japan Science and Technology Agency
2014-2016
Japan Biological Informatics Consortium
2002-2013
Chiba Institute of Technology
2008
SPring-8
2008
Medical College of Wisconsin
2005
National Institute of Advanced Industrial Science and Technology
2005
The University of Tokyo
2005
Osaka University of Pharmaceutical Sciences
2002
Okayama University
1997-1999
The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for current coronavirus disease (COVID-19) pandemic. 3CL protease (3CLpro) plays a pivotal role in processing of viral polyproteins. We report peptidomimetic compounds with unique benzothiazolyl ketone warhead group, which display potent activity against SARS-CoV-2 3CLpro. most inhibitor YH-53 can strongly block replication. X-ray structural analysis revealed that establishes multiple hydrogen bond interactions...
Histone chaperones assemble and disassemble nucleosomes in an ATP-independent manner thus regulate the most fundamental step alteration of chromatin structure. The molecular mechanisms underlying histone chaperone activity remain unclear. To gain insights into these mechanisms, we solved crystal structure functional domain SET/TAF-Ibeta/INHAT at a resolution 2.3 A. We found that formed dimer assumed "headphone"-like Each subunit consisted N terminus, backbone helix, "earmuff" domain. It...
Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the CagA-specific EPIYA-D segment binds to N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders magnitude greater EPIYA-C. This high-affinity binding achieved via cryptic interaction between Phe at +5 position from phosphotyrosine in and a hollow on phosphopeptide-binding floor. Also, duplication EPIYA-C CagA, which increases risk,...
Carbonic anhydrases (CAs) are universal metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO2) and bicarbonate (HCO3-). They involved in various biological processes, including pH control, respiration, photosynthesis. To date, eight evolutionarily unrelated classes CA families (α, β, γ, δ, ζ, η, θ, ι) have been identified. All characterized by an active site accommodating binding a metal cofactor, which is assumed to play central role catalysis. This feature thought...
Non-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure-function relationship. AusE from Aspergillus nidulans PrhA Penicillium brasilianum are two highly homologous Fe(II)/αKG fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as common substrate divergent rearrangement form the spiro-lactone austinol...
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...
Abstract Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There an urgent need development of selective and safe reagents mosquito control. Flavonoids, group chemical substances with variable phenolic structures, such as daidzein, have been suggested potential larvicides less risk to environment. However, mode larvicidal action flavonoids has not elucidated. Results Here, we report that several flavonoids, including...
AndA, an Fe(II)/α-ketoglutarate (αKG)-dependent enzyme, is the key enzyme that constructs unique and congested bridged-ring system of anditomin (1), by catalyzing consecutive dehydrogenation isomerization reactions. Although we previously characterized AndA to some extent, means which facilitates this drastic structural reconstruction have remained elusive. In study, solved three X-ray crystal structures in its apo form complexes with Fe(II), αKG, two substrates. The mutational experiments...
Abstract Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually means single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams X-rays between 0.7 2 Å wavelength. Use longer wavelengths to access the absorption edges biologically important lighter atoms such...
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,...
Native SAD is an emerging phasing technique that uses the anomalous signal of native heavy atoms to obtain crystallographic phases. The method does not require specific sample preparation add scatterers, as light contained in are used marker atoms. most abundant scatterer for SAD, which present almost all proteins, sulfur. However, absorption edge sulfur at low energy (2.472 keV = 5.016 Å), makes it challenging carry out experiments synchrotron beamlines optimized shorter wavelength ranges...
Oxysterol-binding protein (OSBP), which transports cholesterol and phosphatidylinositol 4-monophosphate (PtdIns[4]P) between different organelles, serves as a conserved host factor for the replication of various viruses, OSBP inhibitors exhibit antiviral effects. Here, we determined crystal structure lipid transfer domain human in complex with endogenous cholesterol. The hydrocarbon tail tetracyclic ring interact hydrophobic tunnel OSBP, hydroxyl group forms hydrogen bond network at bottom...
ABSTRACT Nitrification by heterotrophic microorganisms is an important part of the nitrogen cycle in environment. The enzyme responsible for core function nitrification pyruvic oxime dioxygenase (POD). POD a non-heme, Fe(II)-dependent that catalyzes dioxygenation to produce pyruvate and nitrite. To analyze catalytic mechanism POD, crystal structure from Alcaligenes faecalis (AfPOD) was determined at 1.76 Å resolution. homotetramer, subunit homologous those class II aldolases, particular,...
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon (1C) metabolism, catalyzing the reduction of methylenetetrahydrofolate to methyltetrahydrofolate. Interestingly, Sphingobium lignivorans SYK-6, model bacterium for catabolism lignin-derived aromatic compounds, possesses unique MTHFR (S6MTHFR) that catalyzes reverse reaction typical MTHFRs—namely, oxidation However, no direct evidence supports this function. Here, we show S6MTHFR methyltetrahydrofolate and elucidate...
Protein structural information at the atomic resolution is indispensable in search for lead compounds to develop therapeutic drugs various diseases. To meet these demands, high-throughput analysis of utmost importance. X-ray crystallography, which can collect hundreds datasets per day, best tool rapidly obtaining protein information. achieve rapid structure determination, we need overcome two bottlenecks: crystallization and phasing. Here, present our techniques MR-native SAD method using...
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...
Giant viruses are nonstandard with large particles and genomes. While previous studies have shown that their genomes contain various sequences of interest, genes related specifically to natural product biosynthesis remain unexplored. Here we analyze the function structure a terpene synthase encoded by gene giant virus. The enzyme is phylogenetically separated from synthases cellular organisms; however, heterologous expression revealed it still functions as produces cyclic farnesyl...