- Enzyme Structure and Function
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Metabolomics and Mass Spectrometry Studies
- Peroxisome Proliferator-Activated Receptors
- Metabolism and Genetic Disorders
- Mass Spectrometry Techniques and Applications
- Genomics and Phylogenetic Studies
- Micro and Nano Robotics
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- COVID-19 Clinical Research Studies
- Crystallization and Solubility Studies
- Protist diversity and phylogeny
- Polyamine Metabolism and Applications
- Cell Image Analysis Techniques
- Connective tissue disorders research
- Reproductive Biology and Fertility
- Lipid Membrane Structure and Behavior
- Magnetic and Electromagnetic Effects
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Sperm and Testicular Function
Protein Research Foundation
1987-2025
Osaka University
2012-2025
Kitasato University
2025
Sophia University
2020-2021
Institute for Public Relations
2017
Japan Science and Technology Agency
2009-2012
Worldwide Protein Data Bank
2012
Crystal Research (United States)
2012
Kyoto Pharmaceutical University
1994
Kyoto University
1987
Polyamines are known to play important roles in the proliferation and differentiation of many types cells. Although considerable amounts polyamines synthesized stored testes, their remain unknown. Ornithine decarboxylase antizymes (OAZs) control intracellular concentration a feedback manner. OAZ1 OAZ2 expressed ubiquitously, whereas OAZ-t/OAZ3 is specifically germline cells during spermiogenesis. OAZ-t reportedly binds ornithine (ODC) inactivates ODC activity. In prior study, were capable...
The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, resulting subvariants display further evasion antibody escape. An engineered angiotensin-converting enzyme (ACE2) decoy composed of high-affinity ACE2 an IgG1 Fc domain could offer alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum therapeutic potential in rodent models. Here, we...
The trypsin-sensitive cholecystokinin-releasing peptide is a purified from rat pancreatic juice on the basis of its stimulatory activity toward enzyme secretion. We postulate that acts as mediator secretion in response to dietary protein intake and it (designated monitor role intestine) could be responsible for feedback regulation About 20 nmol highly were obtained 800 ml by reverse-phase high performance liquid chromatography. It was then sequenced. comprises 61 amino acid residues (Table...
The complete amino acid sequence of Achromobacter lyticus protease I (EC 3.4.21.50), which specifically hydrolyzes lysyl peptide bonds, has been established. This achieved by analysis the reduced and S-carboxymethylated peptides obtained enzymatic digestion with itself Staphylococcus aureus V8 chemical cleavage cyanogen bromide. consists 268 residues three disulfide have assigned to Cys6-Cys216, Cys12-Cys80, Cys36-Cys58. Comparison other serine proteases bacterial mammalian origins revealed...
Abstract mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized variant, when four mutations were introduced into...
α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated causal role α-synuclein the pathogenesis PD. However, molecular cellular mechanisms toxicity remain elusive. Here, we describe novel phosphorylation site at T64 detailed characteristics post-translational modification. was enhanced both PD models human brains. T64D phosphomimetic mutation led to distinct oligomer formation, structure similar...
High-throughput protein X-ray crystallography offers a significant opportunity to facilitate drug discovery. The most reliable approach is determine the three-dimensional structure of protein-ligand complex by soaking ligand in apo crystals. However, crystals produced conventional crystallization solution are fatally damaged osmotic shock during soaking. To overcome this difficulty, we present novel technique for growing high-concentration hydrogel that completely gellified and exhibits high...
Abstract Long‐chain fatty acids (FAs) with low water solubility require fatty‐acid‐binding proteins (FABPs) to transport them from cytoplasm the mitochondria for energy production. However, precise mechanism by which these recognize various lengths of simple alkyl chains FAs similar high affinity remains unknown. To address this question, we employed a newly developed calorimetric method comprehensively evaluating FAs, sub‐Angstrom X‐ray crystallography accurately determine their 3D...
Antibody labeling has been conducted extensively for structure determination using both X-ray crystallography and electron microscopy (EM). However, establishing target-specific antibodies is a prerequisite applying antibody-assisted structural analysis. To expand the applicability of this strategy, an alternative method developed to prepare antibody complex by inserting exogenous epitope into target. It already demonstrated that Fab NZ-1 monoclonal can form stable with target containing...
Tubulins are critical for the internal organization of eukaryotic cells, and understanding their emergence is an important question in eukaryogenesis. Asgard archaea closest known prokaryotic relatives to eukaryotes. Here, we elucidated apo nucleotide-bound x-ray structures tubulin from hydrothermal living Odinarchaeota (OdinTubulin). The guanosine 5'-triphosphate (GTP)-bound structure resembles a microtubule protofilament, with GTP bound between subunits, coordinating "+" end subunit...
The bacterial cell‐division protein FtsA anchors FtsZ to the cytoplasmic membrane. But how and interact during membrane division remains obscure. We have solved 2.2 Å resolution crystal structure for from Staphylococcus aureus . In crystals, SaFtsA molecules within dimer units are twisted, in contrast straight filament of Thermotoga maritima , half S12–S13 hairpin regions disordered. confirmed that SaFtsZ associate vitro, found GTPase activity is enhanced by interaction with SaFtsA.
Site-2 proteases are a conserved family of intramembrane that cleave transmembrane substrates to regulate signal transduction and maintain proteostasis. Here, we elucidated crystal structures inhibitor-bound forms bacterial site-2 including Escherichia coli RseP. Structure-based chemical modification cross-linking experiments indicated the RseP domains surrounding active center undergo conformational changes expose substrate-binding site, suggesting has gating mechanism substrate entry....
Adult growth hormone deficiency (AGHD) is often accompanied with metabolic dysfunction-associated steatotic liver disease (MASLD). Although some studies reported that MASLD ameliorated by replacement therapy (GHRT), the characteristics of AGHD are associated an improvement hepatic steatosis GHRT remain unknown. We aimed to investigate whether affects lipid accumulation as well biochemical parameters, and investigated association between these parameters (UMIN000044989). Thirty people were...
Site-2 proteases (S2Ps), conserved intramembrane metalloproteases that maintain cellular homeostasis, are associated with chronic infection and persistence leading to multidrug resistance in bacterial pathogens. A structural model of how S2Ps discriminate accommodate substrates could help us develop selective antimicrobial agents. We previously proposed the Escherichia coli S2P RseP unwinds helical substrate segments before cleavage, but mechanism for accommodating a full-length...
Signal transducer and activator of transcription (STAT) family members mediate signaling in the Janus kinase (JAK)–STAT pathway are activated by phosphorylation at a conserved tyrosine residue, resulting dimerization through reciprocal interactions between phosphotyrosine Src homology 2 (SH2) domain. Tyrosine-phosphorylated STAT (pY-STAT) then translocates to nucleus induce expression genes encoding antiviral proteins. Although active functional forms STATs conventionally considered be...
Prostaglandin receptors have been implicated in a wide range of functions, including inflammation, immune response, reproduction, and cancer. Our group has previously determined the crystal structure active-like EP3 bound to its endogenous agonist, prostaglandin E2. Here, we present single-particle cryoelectron microscopy (cryo-EM) human EP3-Gi signaling complex at resolution 3.4 Å. The reveals binding mode Gi structural changes induced by binding. In addition, compare with other subtypes...
The 21-residue peptide α3, which is artificially designed and consists of three repeats 7 residues, known to rapidly assemble into the α-helix nanofiber. However, its molecular structure within fiber has not yet been fully elucidated. Thus, we conducted a thorough investigation fiber's using solid-state NMR other techniques. molecules were found be primarily composed structure, with some regions near C- N-terminal adopting 310-helix structure. Furthermore, it was discovered that β-sheet...
Many bacteria swim in liquid or swarm on surface using the flagellum rotated by a motor driven specific ion flow. The consists of rotor and stator, stator converts energy flow to mechanical rotation. However, pathway mechanism rotation coupled with are still obscure. Here, we determined structures sodium-driven Vibrio , namely PomAB, presence absence sodium ions structure its inhibitor, phenamil, cryo-electron microscopy. following functional analysis revealed pathway, selectivity,...
ABSTRACT The κ-opioid receptor (KOR) is a member of the G protein-coupled (GPCR) family, responsible for modulating cellular responses through transducers such as proteins and arrestins. protein-biased KOR agonists hold promise due to their potential mitigate side effects drug aversion sedation while preserving analgesic antipruritic effects. Here, we shed light on structural dynamics human KOR-G i signaling complex bound with either nalfurafine (a G-protein-biased agonist) or U-50,488H...
We investigate the nucleation rate of protein crystals in presence agarose gel at concentrations between 0.0 and 2.0% (w/v). It was found that promoted number up to a concentration 0.4% (w/v), 0.4 0.8% (w/v) decreased rate. However, increased again by more than 1.0% demonstrating high strength semi-solid gel. propose crystallization method using is powerful for screening conditions.
Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic abundantly found in cardiomyocytes, plays role trafficking fatty acids throughout cellular compartments by reversibly binding intracellular with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) extensively utilized for examining the interaction of ligands proteins. X-ray structure FABP3 was determined presence ANS and revealed detailed ANS-binding mechanism. Furthermore, four water...
ABSTRACT The marine bacterium Vibrio alginolyticus possesses a polar flagellum driven by sodium ion flow. main components of the flagellar motor are stator and rotor. C-ring MS-ring, which composed FliG FliF, respectively, parts Here, we purified an MS-ring FliF–FliG fusion proteins solved near-atomic resolution structure S-ring—the upper part MS-ring—using cryo-electron microscopy. This is first report S-ring from , whereas, previously, only those Salmonella have been reported. reveals...