A5048073780- Enzyme Structure and Function
- Enzyme Production and Characterization
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Protein Structure and Dynamics
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Carbohydrate Chemistry and Synthesis
- Antimicrobial Resistance in Staphylococcus
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Enzyme Catalysis and Immobilization
- Chemical Synthesis and Reactions
- Synthesis of Organic Compounds
- Organic Chemistry Cycloaddition Reactions
- Synthesis and biological activity
- Immune Cell Function and Interaction
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Microbial Metabolism and Applications
- Bacterial biofilms and quorum sensing
- Probiotics and Fermented Foods
National Institute of Advanced Industrial Science and Technology
2017-2024
Burke Medical Research Institute
2017
The University of Tokyo
2008-2015
Tokyo Medical University
2012
Abstract The rapid spread of antibiotic-resistance among pathogenic bacteria poses a serious risk for public health. search novel therapeutic strategies and antimicrobial compounds is needed to ameliorate this menace. bifunctional metalloenzyme CapF an antibacterial target produced by certain essential in the biosynthetic route capsular polysaccharide, mucous layer on surface bacterium that facilitates immune evasion infection. We report first inhibitor from Staphylococcus aureus , which was...
Abstract Human P-cadherin is a cell adhesion protein of the family classical cadherins, overexpression which correlated with poor prognosis in various types cancer. Antibodies inhibiting cell-cell mediated by show clear therapeutic effect, although mechanistic basis explaining their effectiveness still unclear. Based on structural, physicochemical, and functional analyses, we have elucidated molecular mechanism disruption antibodies targeting human P-cadherin. Herein studied three different...
CapE is an essential enzyme for the synthesis of capsular polysaccharide (CP) pathogenic strains Staphylococcus aureus . Herein we demonstrate that a 5‐inverting 4,6‐dehydratase enzyme. However, in absence downstream enzymes, catalyzes additional reaction (5‐back‐epimerization) affording by‐product under thermodynamic control. Single‐crystal X‐ray crystallography was employed to identify structure by‐product. The structural analysis reveals network coordinated motions away from active site...
Enzymes synthesizing the bacterial CP (capsular polysaccharide) are attractive antimicrobial targets. However, we lack critical information about structure and mechanism of many them. In an effort to reduce that gap, have determined three different crystal structures enzyme CapE human pathogen Staphylococcus aureus. The reveals is a member SDR (short-chain dehydrogenase/reductase) super-family proteins. assembles in hexameric complex stabilized by major contact surfaces between protein...
Backbone circularization of protein is a powerful method to improve its structural stability. In this paper, we presumed that tight connection leads much higher Therefore, designed circularized variants granulocyte-colony stimulating factor (G-CSF) with structurally optimized terminal connection. To estimate the appropriate length connection, surveyed Protein Data Bank find local structures as model for connecting segment. We set library composed "helix–loop–helix," subsequently selected...
Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that upon binding to its receptor (EGFR) stimulates proliferative signaling, especially in colon cancer cells. Here, we describe three-dimensional structure EPR antibody (the 9E5(Fab) fragment) presence and absence EPR. Among six complementarity-determining regions (CDRs), CDR1-3 light chain CDR2 heavy predominantly recognize In particular, CDR3 dramatically moves with cis-trans isomerization Pro(103). A molecular...
CP (capsular polysaccharide) is an important virulence factor during infections by the bacterium Staphylococcus aureus. The enzyme CapF attractive therapeutic candidate belonging to biosynthetic route of pathogenic strains S. In present study, we report two independent crystal structures in open form apoenzyme. a homodimer displaying characteristic dumb-bell-shaped architecture composed domains. N-terminal domain (residues 1–252) adopts Rossmann fold short-chain dehydrogenase/reductase...
Human P-cadherin is a promising therapeutic target against cancer. However, its characterization at the molecular level still lacking. We report that human associated irreversibly in distinct dimer configuration. Unexpectedly, divalent cation Ca2+ was not necessary for dimerization, although it greatly stabilized protein–protein complex.
Therapeutic IgG becomes unstable under various stresses in the manufacturing process. The resulting non-native molecules tend to associate with each other and form aggregates. Because such aggregates not only decrease pharmacological effect but also become a potential risk factor for immunogenicity, rapid analysis of aggregation is required quality control therapeutic IgG. In this study, we developed homogeneous assay using AlphaScreen AF.2A1. AF.2A1 25-residue artificial protein that binds...
Backbone circularization is an effective technique for protein stabilization. Here, we investigated the effect of a connector, engineered segment that connects two termini, on conformational stability previously designed circularized variants granulocyte colony-stimulating factor (G-CSF). Heat tolerance and chemical denaturation analyses revealed aggregation resistance thermodynamic were superior to those linear G-CSF. Crystal structure molecular dynamics (MD) simulation most...
Capsular polysaccharides (CPs) are important virulence factors of Staphylococcus aureus. The biosynthesis type 5 and 8 CPs (CP5 CP8), which produced by most clinical isolates S. aureus, is catalyzed 16 CP-assembling proteins. One these proteins the enzyme CapF, catalyzes synthesis UDP-N-acetyl-l-fucosamine, a component both CP5 CP8. Here, cloning, expression, purification, crystallization diffraction analysis CapF reported. Optimization conditions differential scanning calorimetry afforded...
IFNγ can initiate immune responses by inducing the expression of major histocompatibility complex molecules, suggesting its potential for cancer immunotherapy. However, it also has an immunosuppressive function that limits application as a therapeutic agent. characteristic domain-swapped dimer structure with two six α-helices exchanged each other. As we hypothesized contrasting functions could be attributed to unique structure, designed monomeric transforming wild-type IFNγ. We conjectured...