- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Microbial Natural Products and Biosynthesis
- Hormonal Regulation and Hypertension
- Crystallography and molecular interactions
- Peroxisome Proliferator-Activated Receptors
- Inorganic Chemistry and Materials
- Chemical Synthesis and Characterization
- Plant biochemistry and biosynthesis
- MXene and MAX Phase Materials
- Heart Failure Treatment and Management
- Receptor Mechanisms and Signaling
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Rare-earth and actinide compounds
- Adrenal Hormones and Disorders
- Fungal Biology and Applications
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Synthetic Organic Chemistry Methods
- Inflammatory mediators and NSAID effects
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Ferroelectric and Piezoelectric Materials
University of California, Los Angeles
2017-2025
University of California System
2018
Film Independent
2017
Okayama University
2010-2017
Broad Center
2017
Yokohama National University
1969-2012
National Institute for Land and Infrastructure Management
2006-2012
Tokuyama (Japan)
1996-2010
Keele University
2008
Ministry of Land, Infrastructure and Transport
2006
We studied the role of non‐selective type (ET 14 ) endothelin (ET) receptor in vasculature, using a ligand specific to ET receptor, [Glu 9 ]‐sarafotoxin S6b ([Glu ]SRTb). Endothelium‐containing rat thoracic aorta possessed binding sites for 125 I‐[Glu ]SRTb, which were almost eliminated by removal endothelium, while ET‐3‐specific not detected endothelium‐intact aorta. Only was membranes from endothelium porcine ]SRTb exerted only vasodilation aortic ring. These findings indicate that...
The first layered nitride superconductor is reported! intercalation of lithium into the compound β‐ZrNCl (which shown on inside front cover this issue) results in electron transfer from to ZrN layers and conversion semiconducting a black metallic with superconducting transition temperature around 12.5 K. Interesting parallels copper oxide superconductors alkali‐metal doped fullerene should provide insight mechanism high‐ T c superconductivity.
To examine the effect of age on secretion and action human atrial natriuretic polypeptide (hANP), we compared plasma cGMP concentrations in 19 normal young (24–28 yr old) 31 elderly (64–91 men. The mean basal hANP level was 25 ± 5 (±sem) pg/ml men 120 22 (P < 0.01). molecular size an aged man similar to that ahANP. responses iv infusion 500 ml 0.15 M NaCl also compared. Mean increased significantly both groups, response exaggerated However, increases during loading were groups. We conclude...
The pericyclases are a growing superfamily of enzymes that catalyze pericyclic reactions. We report pericyclase IccD catalyzing an inverse-electron demand Diels-Alder (IEDDA) reaction with rate acceleration 3 × 105-fold in the biosynthesis fungal natural product ilicicolin H. demonstrate is highly periselective toward IEDDA cycloaddition over competing normal electron (NEDDA) from ambimodal transition state. A predicted flavoenzyme IccE was identified to epimerize 8- epi-ilicicolin H H, step...
Diels–Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing of enzymatic intramolecular have been discovered, intermolecular Diels–Alderases rarely described. Here, we report an hetero-Diels–Alder reaction in biosynthesis tropolonic sesquiterpenes and functionally characterize EupfF as first fungal hetero-Diels–Alderase. We demonstrate catalyzed dehydration a hydroxymethyl-containing tropolone (5) generate...
Pyridoxal 5′-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), useful building blocks pharmaceuticals. In this study, starting with biosynthesis of fusarilin A, we discovered a family PLP-dependent that can facilitate tandem carbon–carbon forming steps to catalyze an overall [3 + 2]-annulation. first step, cycloleucine synthases...
Pericyclases are an emerging family of enzymes catalyzing pericyclic reactions. A class lipocalin-like recently characterized as Diels–Alderases (DAses) catalyze decalin formation through intramolecular Diels–Alder (IMDA) reactions between electron-rich dienes and electron-deficient dienophiles. Using this enzyme a beacon for genome mining, we discovered biosynthetic gene cluster from Penicillium variabile identified that it encodes the biosynthesis varicidin (1), new antifungal natural...
Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The of 1 is tetracyclic, cage-like, oxygenated sesquiterpene connected dimethylcadaverine via C–N bond acylated with 5,5-dimethyl-l-pipecolate. roles all are established...
The sensory bundle of vertebrate cochlear hair cells consists actin-containing stereocilia that are thought to bend at their ankle during mechanical stimulation. Stereocilia have dense rootlets extend through the region anchor them into cuticular plate. Because this may be important in stiffness and durability prolonged stimulation high frequencies, we investigated structure dimensions relative apical (low-frequency) basal (high-frequency) regions rodent cochleae using light electron...
Human peroxisome proliferator-activated receptors (hPPARs) are ligand-dependent transcription factors that control various biological responses, and there three subtypes: hPPARα, hPPARδ, hPPARγ. We report here α-substituted phenylpropanoic acid-type hPPAR agonists with similar structure bind to the ligand binding domain (LBD) in different conformations, depending on receptor subtype. These results might indicate pockets have multiple points can be utilized accommodate structurally flexible ligands.
The pentasubstituted pyridine natural products harzianopyridone and atpenins are potent inhibitors of mitochondrial complex II. We identified the pathways these compounds from their fungal producers uncovered that biosynthetic steps require multiple iterative enzymes. In particular, a methyltransferase flavin-dependent monooxygenase used iteratively to introduce C5 C6 methoxy groups. pathway unexpectedly requires installation removal an N-methoxy group, which is proposed be directing group...
We uncovered the biosynthetic pathway of lethal mycotoxin 3-nitropropanoic acid (3-NPA) from koji mold Aspergillus oryzae. The gene cluster (BGC) 3-NPA, which encodes an amine oxidase and a decarboxylase, is conserved in many fungi used food processing, although most strains have not been reported to produce 3-NPA. Our discovery will lead efforts that improve safety profiles these indispensable microorganisms making food, alcoholic beverages, seasoning.
Fungal enzymes containing domain of unknown function (DUF) 3328 have been implicated in the oxidative maturation ribosomally synthesized and post-translationally modified peptides (RiPPs). We report here functional characterization one such enzyme, AprY, involved biosynthesis RiPP asperipin-2a. Biochemical reconstitution AprY showed enzyme catalyzes two consecutive C-O cross-linking reactions between tyrosines beta-carbons residues core hexapeptide. The side-chain macrocyclization activities...
The responses of plasma cortisol, aldosterone, dehydroepiandrosterone (DHEA) and sulfate (DHEA-S) to graded ACTH infusions (from 50 mU/h 1,000 mU/h) in elderly subjects were compared with those young subjects. There no significant differences between terms the levels cortisol during infusion. increment median serum increase observed was also equal that found Plasma aldosterone concentration showed a gradual response infusion both individuals. difference aged Significant increases DHEA...