- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Urinary Bladder and Prostate Research
- Protein Structure and Dynamics
- Biochemical and Structural Characterization
- Lipid Membrane Structure and Behavior
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Microbial Natural Products and Biosynthesis
- Antibiotic Resistance in Bacteria
- Prostate Cancer Diagnosis and Treatment
- Trace Elements in Health
- Renal cell carcinoma treatment
- Clostridium difficile and Clostridium perfringens research
- Bone health and osteoporosis research
- Probiotics and Fermented Foods
- Autoimmune Bullous Skin Diseases
- Drug Transport and Resistance Mechanisms
- Urologic and reproductive health conditions
- Bone and Joint Diseases
- Glycosylation and Glycoproteins Research
Suita Tokushukai Hospital
2022-2024
Paul Scherrer Institute
2018-2023
Kyushu University
2008-2023
Universidade Nova de Lisboa
2013-2020
Institute of Structural and Molecular Biology
2004-2019
University of Leeds
2004-2019
Toyonaka Municipal Hospital
2015-2018
Trinity College Dublin
2015-2017
University Hospitals of Cleveland
2017
Université Libre de Bruxelles
2015
The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 which arranged in two inverted repeats five helices. structures outward-facing open substrate-bound occluded conformations were solved, showing how cavity closes upon binding substrate....
Abstract Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs) 1 . A photon absorbed 11- cis retinal chromophore rhodopsin, which isomerizes within 200 femtoseconds to all- trans conformation 2 , thereby initiating cellular signal transduction processes that ultimately lead vision. However, intramolecular mechanism photoactivated induces activation events inside remains experimentally unclear. Here we use ultrafast time-resolved crystallography at...
Chloride transport by microbial rhodopsins is an essential process for which molecular details such as the mechanisms that convert light energy to drive ion pumping and ensure unidirectionality of have remained elusive. We combined time-resolved serial crystallography with spectroscopy multiscale simulations elucidate mechanism a chloride-pumping rhodopsin structural dynamics throughout cycle. traced transient anion-binding sites, obtained evidence how used in mechanism, identified steric...
The lipid cubic phase (LCP) continues to grow in popularity as a medium which generate crystals of membrane (and soluble) proteins for high-resolution X-ray crystallographic structure determination. To date, the PDB includes 227 records attributed LCP or meso method. Among listings are some highest profile proteins, including β2-adrenoreceptor-Gs protein complex that figured award 2012 Nobel Prize Chemistry Lefkowitz and Kobilka. most successful protocol date uses glass sandwich...
Here, a method for presenting crystals of soluble and membrane proteins growing in the lipid cubic or sponge phase situ diffraction data collection at cryogenic temperatures is introduced. The dispenses with need technically demanding inefficient crystal-harvesting step that an integral part meso crystals. Crystals are dispersed bolus mesophase sandwiched between thin plastic windows. contains tens to hundreds crystals, visible in-line microscope macromolecular crystallography synchrotron...
Selective coupling of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) to specific Gα-protein subtypes is critical transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center this transduction event lies formation a signaling complex between receptor protein. We report crystal structure light-sensitive GPCR rhodopsin bound an engineered mini-Go The conformation identical all previous structures...
To determine the angiogenic profiles in bladder of patients with pain syndrome (BPS)/interstitial cystitis (IC), and to evaluate relationship between these associated clinical features including pelvic glomerulations.Angiogenesis components are important chronic inflammatory disease. High levels vascular endothelial growth factor (VEGF) have been shown induce immature angiogenesis, where microvessels insufficient coverage pericytes, resulting haemorrhagic vessels. Biopsy specimens from 30...
The expression of two Enterococcus faecalis virulence-related proteases, gelatinase (GelE) and serine protease (SprE), is positively regulated by a quorum-sensing system encoded the fsr gene cluster. In this system, E. secretes an autoinducing peptide, biosynthesis-activating pheromone (GBAP), which triggers FsrC-FsrA two-component regulatory controlling transcripts, fsrBDC gelE-sprE. present study, we screened actinomycete metabolites for inhibitors quorum sensing. was cultured with each...
ABSTRACT Expression of virulence-related extracellular proteases, gelatinase, and serine protease Enterococcus faecalis is regulated by a quorum-sensing system encoded the fsr gene cluster. In this study, 23.9-kb chromosomal deletion containing cluster region was found to be present in majority (79%) gelatinase-negative clinical isolates E. from urine.
Enterococcus faecalis fsr quorum sensing (QS) involves an 11-residue cyclic peptide named gelatinase biosynthesis-activating pheromone (GBAP) that autoinduces two pathogenicity-related extracellular proteases in a cell density-dependent fashion. To identify anti-pathogenic agents target QS signaling, antagonists of GBAP were created by our unique drug design approach based on reverse alanine scanning. First all, receptor-binding scaffold (RBS), [Ala(4,5,6,8,9,11)]Z-GBAP, was created, which...
Purpose: Fragility fracture risk in patients with prostate cancer is an important issue. The purpose of this study was to accurately assess the impact androgen deprivation therapy on lumbar spine bone loss using quantitative computed tomography a propensity-matched cohort cancer. Materials and Methods: Eighty-one who underwent for 1 year were included. Thirty-nine these successfully 39 68 from control group robot-assisted radical prostatectomy without therapy. Volumetric mineral density...
Lipoproteins are present in a wide variety of bacteria and anchored to membranes through lipids attached the N-terminal cysteine. The Lol system Escherichia colimediates membrane-specific localization lipoproteins. Aspartate at position 2 functions as avoidance signal causes retention lipoproteins inner membrane, whereas having residues other than aspartate released from membrane localized outer by system. Phospholipid:apolipoprotein transacylase, Lnt, catalyzes last step lipoprotein...
Enterococcus faecalis V583 is a vancomycin-resistant clinical isolate which belongs to the hospital-adapted clade, CC2. This strain harbours several factors that have been associated with virulence, including fsr quorum-sensing regulatory system known control expression of GelE and SprE proteases. To discriminate between genes directly regulated by Fsr, those indirectly as result protease or activity, we compared gene in isogenic mutants variously defective either Fsr quorum sensing...
Quorum sensing inhibitor (QSI) has been attracting attention as anti-virulence agent which disarms pathogens of their virulence rather than killing them. QSI marking cyclic peptide-mediated QS in Gram-positive bacteria is an effective tool to overcome the crisis antibiotic-dependent chemotherapy due emergence drug resistance strain, e.g., methicillin resistant Staphylococcus aureus (MRSA) and Vancomycin Enterococci (VRE). From a semi-large-scale screening thus far carried out, two Epoxide...
No AccessJournal of UrologyInvestigative Urology1 May 2009Sesquiterpene Lactone Parthenolide Ameliorates Bladder Inflammation and Overactivity in Cyclophosphamide Induced Rat Cystitis Model by Inhibiting Nuclear Factor-κB Phosphorylationis accompanied byLearning to Control Hiroshi Kiuchi, Tetsuya Takao, Keisuke Yamamoto, Jiro Nakayama, Yasushi Miyagawa, Akira Tsujimura, Norio Nonomura, Akihiko Okuyama KiuchiHiroshi Kiuchi , TakaoTetsuya Takao YamamotoKeisuke Yamamoto NakayamaJiro Nakayama...
This work reports the evolutionary relationships, amplified expression, functional characterization and purification of putative allantoin transport protein, PucI, from Bacillus subtilis. Sequence alignments phylogenetic analysis confirmed close relationships between PucI membrane proteins nucleobase-cation-symport-1 family secondary active transporters. These include sodium-coupled hydantoin Mhp1, Microbacterium liquefaciens, related bacteria, fungi plants. Membrane topology predictions for...
Staphylococcus warneri ISK-1 produces a lantibiotic, nukacin ISK-1. The gene cluster consists of at least six genes, nukA, -M, -T, -F, -E, and -G, two open reading frames, ORF1 ORF7 (designated nukH). Sequence comparisons suggested that NukF, -H contribute to immunity We investigated the levels recombinant Lactococcus lactis expressing nukFEG nukH against co-expression resulted in high degree immunity. expression either or conferred partial These results suggest NukH contributes...
Staphylococcus aureus and Enterococcus faecalis employ cyclic peptide-mediated quorum sensing (QS) systems, termed agr fsr respectively, to regulate the expression of a series virulence genes. To identify inhibitors (QSIs) that target agr/fsr an efficient screening system was established. In addition gelatinase-induction assay examine E. QS, use S. reporter strain carries luciferase green fluorescence protein genes under P3 promoter facilitated development high-throughput screen (HTS) for...
Siamycin I disrupts growth and quorum sensing in Enterococcus faecalis. Using purified intact protein, we demonstrate here that membrane sensor kinase FsrC is a direct target of siamycin I, reducing pheromone-stimulated autophosphorylation activity by up to 91%. Inhibition was non-competitive with ATP as substrate. Other ATP-binding enzymes were also inhibited, including nine other kinases E. faecalis, Rhodobacter sphaeroides PrrB, porcine Na(+)-dependent ATPase the catalytic subunit bovine...