Publications by authors named "M Ikeguchi"
Synergistic Activation of TLR7 and 8 Mediated by Reduction of Electrostatic Repulsion.
Chem Pharm Bull (Tokyo)
November 2024
Toll-like receptors (TLRs) play central roles in innate immune defense against infection by binding to microbial molecules. TLR7 and TLR8 are highly homologous sensors with an RNA ligand preference for single-stranded RNA (ssRNA). Recent works reveal that these TLR sense degradation products of RNA at two distinct binding sites, designated 1st site and 2nd site, rather than long ssRNA.
View Article and Find Full Text PDFNa-V-ATPase inhibitor curbs VRE growth and unveils Na pathway structure.
Nat Struct Mol Biol
November 2024
Vancomycin-resistant Enterococcus faecium (VRE) is a major cause of nosocomial infections, particularly endocarditis and sepsis. With the diminishing effectiveness of antibiotics against VRE, new antimicrobial agents are urgently needed. Our previous research demonstrated the crucial role of Na-transporting V-ATPase in Enterococcus hirae for growth under alkaline conditions.
View Article and Find Full Text PDFMacaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates how changes in protein structure, such as mutations, affect the binding of drug inhibitors, specifically methotrexate (MTX), to dihydrofolate reductase (DHFR).
- Molecular dynamics simulations and Markov state modeling were used to analyze the binding thermodynamics and kinetics for both wild-type and mutant DHFR variants.
- Findings reveal that mutations can destabilize the primary binding site, leading to increased binding at secondary sites, challenging traditional models of drug sensitivity and suggesting a more complex binding landscape.
Article Synopsis
- Privalov and colleagues studied how hydration enthalpy and entropy change when the protein ubiquitin unfolds, using measurements from various model compounds transitioning from gas to water.
- They applied statistical-mechanics theory with molecular and atomistic models to estimate these changes, finding their results align well with Privalov's estimates.
- The study emphasizes the importance of the hydrophobic effect in protein folding and presents new insights into understanding its weakening at lower temperatures, while also addressing issues with measuring changes in enthalpy and entropy at low pH and proposing methods for calculations at neutral pH.