A5043599525- Vitamin D Research Studies
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Estrogen and related hormone effects
- Signaling Pathways in Disease
- Biotin and Related Studies
- Toxin Mechanisms and Immunotoxins
- Peptidase Inhibition and Analysis
- Heat shock proteins research
- Retinoids in leukemia and cellular processes
- Biochemical and Structural Characterization
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Hormonal Regulation and Hypertension
- Alzheimer's disease research and treatments
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Enzyme Production and Characterization
- Proteins in Food Systems
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Insect and Pesticide Research
- Antioxidant Activity and Oxidative Stress
Tokyo Medical and Dental University
2013-2022
Ochanomizu University
2022
The University of Tokyo
1996-2018
Hokkaido University
2015
The Open University of Japan
2015
Kyoto University
1991-2015
MED Institute
2013
Tokyo Medical University
2011
Showa Pharmaceutical University
2009
Japan Science and Technology Agency
2004-2008
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of melittin bound to perdeuterated dodecylphosphocholine micelles as studied by two-dimensional NMR and distance geometry calculationsFuyuhiko Inagaki, Ichio Shimada, Ken Kawaguchi, Masahiko Hirano, Isao Terasawa, Teikichi Ikura, Nobuhiro GoCite this: Biochemistry 1989, 28, 14, 5985–5991Publication Date (Print):July 11, 1989Publication History Published online1 May 2002Published inissue 11 July...
Abstract Autophosphorylation of amino-acid residues is part the folding process various protein kinases. Conventional chemical screening mature kinases has missed inhibitors that selectively interfere with process. Here we report a cell-based assay evaluates inhibition kinase at transitional state during and identify intermediate-selective inhibitor dual-specificity tyrosine-phosphorylation-regulated 1A (DYRK1A), which refer to as FINDY. FINDY suppresses intramolecular autophosphorylation...
The X-ray crystal structures of the rat VDR ligand-binding domain complexed with 19-norvitamin D compounds that contain an adamantyl substituent at side-chain terminus, 2a (ADTT), 2b (ADNY), and 2c (ADMI4) a coactivator peptide derived from DRIP205 are reported. These show series partial agonistic (10-75% efficacy)/antagonistic activities. All these receptors crystallized in canonical active conformation, regardless their activity profiles. bulky side chain does not crowd helix 12 but...
To identify novel vitamin D receptor (VDR) ligands that induce a architecture within the ligand-binding pocket (LBP), we have investigated eight 22-butyl-1α,24-dihydroxyvitamin D3 derivatives (3−10), all having butyl group as branched alkyl side chain. We found 22S-butyl-20-epi-25,26,27-trinorvitamin derivative 5 was potent VDR agonist, whereas corresponding compound 4 with natural configuration at C(20) antagonist. Analogues full chain were less and whether they agonists or antagonists...
Excessive angiogenesis contributes to numerous diseases, including cancer and blinding retinopathy. Antibodies against vascular endothelial growth factor (VEGF) have been approved are widely used in clinical treatment. Our previous studies using SRPIN340, a small molecule inhibitor of SRPK1 (serine-arginine protein kinase 1), demonstrated that is potential target for the development antiangiogenic drugs. In this study, we solved structure bound SRPIN340 by X-ray crystallography. Using...
The secondary bile acid lithocholic (LCA) and its derivatives act as selective modulators of the vitamin D receptor (VDR), although their structures fundamentally differ from that natural hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3)]. Here, we have determined crystal ligand-binding domain rat VDR (VDR-LBD) in ternary complexes with a synthetic partial peptide coactivator MED1 (mediator RNA polymerase II transcription subunit 1) four ligands, LCA, 3-keto LCA acetate, propionate, goal...
Abstract In our previous paper we reported the conformation of melittin bound to perdeuterated dodecylphosphocholine micelles as studied by 1 H NMR experiment and distance geometry calculation. No hydrogen bonds were taken into consideration explicitly in However, mostly α‐helical conformations obtained results calculation even with no assumed bonds. present refined incorporating suggested As a result, melittin, which was consistent both data additional bonding data. The rod also has kink at...
DNA damage is increased in Alzheimer's disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, human AD postmortem brains. The inhibits accumulation Ku70 to foci double strand break (DSB), impairs repair eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis...
Effects of proline isomerizations on the equilibrium unfolding and kinetic refolding staphylococcal nuclease were studied by circular dichroism in peptide region (225 nm) fluorescence spectra a tryptophan residue. For this purpose, four single mutants (P11A, P31A, P42A, P56A) multiple (P11A/P47T/P117G, P11A/P31A/P47T/P117G, P11A/P31A/P42A/P47T/P117G, P11A/P31A/P42A/P47T/P56A/P117G) constructed. These mutants, together with double for Pro47 Pro117 constructed our previous study, cover all six...
Vitamin D receptor (VDR) ligands are therapeutic agents that used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism have immense potential as autoimmune diseases, cancers, cardiovascular diseases. However, major side effect VDR ligands, development hypercalcemia, limits their expanded use. To develop tissue-selective modulators, we designed vitamin analogues with an adamantane ring at chain terminal, which would interfere helix 12, activation function 2,...
Peptidyl-prolyl isomerase (PPIase) activity is exhibited by many proteins belonging to the PPIase family. However, catalytic mechanism of this remains be completely elucidated. Here, we selected human FK506-binding protein 12 (FKBP12) as model and investigated nature amino acid residues essential for activity. The crystal structures several complexes with short peptides revealed that Asp37, Arg42, Phe46, Val55, Trp59, Tyr82 in substrate-binding cavity FKBP12 appear play key roles Each these...
The vitamin D receptor (VDR), a member of the nuclear superfamily, functions as ligand-dependent transcription factor for various genes. Hereditary D-resistant rickets (HVDRR), an autosomal recessive disease, is caused by mutations in VDR. In particular, missense R274L and W286R ligand-binding domain VDR can severely reduce or even eliminate natural hormone responsiveness. Here, we report crystal structure analysis R270L W282R mutants rat (human W286R, respectively) complex with synthetic...
The equilibrium and kinetics of the unfolding refolding authentic recombinant human α-lactalbumin, latter which had an extra methionine residue at N-terminus, were studied by circular dichroism spectroscopy, results compared with for bovine goat α-lactalbumins obtained in our previous studies. As observed proteins, presence protein remarkably destabilized native state, destabilization was entirely ascribed to increase rate unfolding. thermodynamic stability state against unfolded lower,...
The Alzheimer's disease-related protein, tau, aggregates into neurofibrillary tangles when it is hyperphosphorylated. amino acid sequence included in the third repeat (R3) of microtubule-binding region suspected to be main factor for tau aggregation. Here, we synthesized a 31-residue oligopeptide, corresponding R3 region, and characterized its aggregation propensity under various conditions. This peptide aggregated even absence an aggregation-inducing molecule at low salt concentration,...
Full activation of T cells and differentiation into effector are essential for many immune responses require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to recruits protein-tyrosine kinases its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation tyrosine, proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream Shc (Gads), p85 subunit phosphoinositide 3-kinase may bind pYMNM (where pY is phosphotyrosine)...
The complex of barnase (bn) and barstar (bs), which has been widely studied as a model for quantitative analysis protein-protein interactions, is significantly destabilized by single mutation, namely, bs Asp39 --> Ala, corresponds to change 7.7 kcal x mol(-1) in the free energy binding. However, there no structural information available explain such drastic destabilization. In present study, we determined structure mutant at 1.58 A resolution X-ray crystallography. was similar wild-type...
Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein (Grb2) specifically recognizes pY-X-N-X, whereas phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding pY site CD28 (pY-M-N-M) by PI3K and Grb2 through their is key step triggers transduction for T cell activation...