A5077817293- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- RNA modifications and cancer
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Enzyme Production and Characterization
- Crystallization and Solubility Studies
- Molecular Sensors and Ion Detection
- Erythrocyte Function and Pathophysiology
- Porphyrin Metabolism and Disorders
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Heme Oxygenase-1 and Carbon Monoxide
- DNA and Nucleic Acid Chemistry
- Enzyme Catalysis and Immobilization
- ATP Synthase and ATPases Research
- Signaling Pathways in Disease
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
Tohoku University
2016-2025
RIKEN Center for Biosystems Dynamics Research
2018-2024
RIKEN Center for Integrative Medical Sciences
2003-2021
Kumamoto Medical Center
2021
Délégation Paris 7
2018
Institut Jacques Monod
2018
Merck Institute for Science Education
2018
Hudson Institute
2018
CARE Canada
2018
Université Paris Cité
2018
Abstract Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline indole moiety, respectively, which target the main protease (M pro ). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, immunocytochemistry show both compounds to block infectivity of EC 50 values 15 ± 4 4.2 0.7 μM respectively. Remdesivir permitted viral breakthrough at high...
The concave surface of the crescent-shaped Bin-amphiphysin-Rvs (BAR) domain is postulated to bind cell membrane induce deformation a specific curvature. Rac binding (RCB) domain/IRSp53-MIM homology (IMD) has dimeric structure that similar BAR domain; however, RCB domain/IMD "zeppelin-shaped" dimer. Interestingly, IRSp53 possesses binding, and actin filament abilities. Here we report induces independent filaments in Rac-dependent manner. In contrast domain, did not cause long tubulation...
tmRNA and small protein B (SmpB) are essential trans-translation system components. In the present study, we determined crystal structure of SmpB in complex with entire tRNA domain from Thermus thermophilus. Overall, ribonucleoprotein (tRNP) mimics a long-variable-arm (class II tRNA) canonical L-shaped tertiary structure. The terminus corresponds to acceptor T arms, or upper part, tRNA. On other hand, simulates lower anticodon D stems, Intriguingly, several amino acid residues collaborate...
Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology a variety renal diseases, such as CKD, AKI, steroid–resistant nephrotic syndrome. Antioxidant therapies being investigated, but clinical outcomes have yet to be determined. Recently, we reported that newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level survival fibroblasts from patients with mitochondrial disease. MA-5 modulates synthesis...
Interleukin (IL)-15 is a pleiotropic cytokine that plays pivotal role in both innate and adaptive immunity. IL-15 unique among cytokines due to its participation trans signaling mechanism which receptorα (IL-15Rα) from one subset of cells presents neighboring IL-2Rβ/γc-expressing cells. Here we present the crystal structure complex with sushi domain IL-15Rα. The reveals theα receptor-binding epitope adopts conformation, which, together amino acid substitutions, permits specific interactions...
X-Ray analysis of the co-crystallization compound formed between tetraethylresorcin[4]arene 1 and tetraethylammonium ion, Et4N+·1·1–·8H2O·2EtOH, has shown that two 'head-to-head' arranged resorcinarenes are linked by eight water molecules encapsulate a ion within cavity via cation–π interactions.
SARS-CoV-2-specific CD8+ T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific converted to functionally competent cross-reactive SARS-CoV-2. Here, we identified the HLA-A24-high binding, immunodominant epitopes SARS-CoV-2 spike region that can be recognized by seasonal coronavirus-specific from HLA-A24+ UHDs. Cross-reactive were clearly reduced patients with hematological malignancy, who usually...
Abstract Serine hydroxymethyltransferase (SHMT) produces 5,10-methylenetetrahydrofolate (CH 2 -THF) from tetrahydrofolate with serine to glycine conversion. SHMT is a potential drug target in parasites, viruses and cancer. (+)-SHIN-1 was developed as human inhibitor for cancer therapy. However, the of an antibacterial unknown. Here, we show that bacteriostatically inhibits growth Enterococcus faecium at 50% effective concentration 10 –11 M synergistically enhances activities several...
X-Ray analysis of the molecular complex formed between neurotransmitter acetylcholine (ACh) and resorcin[4]arene, ACh + .resorcinarene.Cl - .H 2 O shows that molecule is captured by macrocyclic resorcinol tetramer through multiple cation–π interactions quaternary trimethylammonium group four π-rings cavitand.
Abstract Recent advances have fundamentally changed the ways in which synthetic amino acids are incorporated into proteins, enabling their efficient and multiple-site incorporation, addition to 20 canonical acids. This development provides opportunities for fresh approaches toward addressing fundamental problems bioengineering. In present study, we showed that structural stability of proteins can be enhanced by integrating bulky halogenated at multiple selected sites. Glutathione S...
Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, mechanism by which conformational pump an anion to achieve unidirectional transport, from extracellular side cytoplasmic side, anion-pumping remains enigmatic. We collected...
We generated SARS-CoV-2 variants resistant to three main protease (M pro ) inhibitors (nirmatrelvir, TKB245, and 5h), by propagating the ancestral WK521 WT in VeroE6 TMPRSS2 cells with increasing concentrations of each inhibitor examined their structural virologic profiles. A predominant E166V-carrying variant (SARS-CoV-2 E166V ), which emerged when passaged nirmatrelvir proved be two inhibitors. recombinant was but sensitive 5h. X-ray study showed that dimerization M severely hindered...
The Rac-specific guanine nucleotide exchange factor (GEF) Asef is activated by binding to the tumor suppressor adenomatous polyposis coli mutant, which found in sporadic and familial colorectal tumors. This involved migration of cells. GEFs for Rho family GTPases contain Dbl homology (DH) domain pleckstrin (PH) domain. When resting state, GEF activity DH-PH module intramolecularly inhibited an unidentified mechanism. has a Src 3 (SH3) addition module. In present study, three-dimensional...
The DNA polymerase processivity factor of the Epstein-Barr virus, BMRF1, associates with catalytic subunit, BALF5, to enhance and exonuclease activities holoenzyme. In this study, crystal structure C-terminally truncated BMRF1 (BMRF1-DeltaC) was solved in an oligomeric state. molecular BMRF1-DeltaC shares structural similarity other factors, such as herpes simplex virus UL42, cytomegalovirus UL44, human proliferating cell nuclear antigen. However, oligomerization architectures these proteins...
The clostridial collagenases G and H are multidomain proteins. For collagen digestion, the domain arrangement is likely to play an important role in binding hydrolysis. In this study, full-length collagenase protein from Clostridium histolyticum was expressed Escherichia coli purified. N-terminal amino acid of purified Ala31. showed enzymatic activity against azocoll as a substrate. To investigate Ca(2+) providing structural stability H, biophysical measurements were conducted using...