The crystal structure of (4S)-limonene synthase from Mentha spic ata, a metal ion-dependent monoterpene cyclase that catalyzes the coupled isomerization and cyclization geranyl diphosphate, is reported at 2.7-A; resolution in two forms liganded to substrate intermediate analogs, 2-fluorogeranyl diphosphate 2-fluorolinalyl respectively. implications these findings are described for domain interactions homodimer changes diphosphate-metal ion coordination binding conformation course multistep reaction.

Radioresistance is a major cause of decreasing the efficiency radiotherapy for non-small cell lung cancer (NSCLC). To understand radioresistance mechanisms in NSCLC, we focused on radiation-induced Notch-1 signaling pathway involved critical fate decisions by modulating proliferation. In this study, investigated use Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity NSCLC cells, NCI-H1299 and NCI-H460, with different levels radioresistance....

Calsequestrin, the major calcium storage protein of both cardiac and skeletal muscle, binds releases large numbers Ca2+ ions for each contraction relaxation cycle. Here we show that two crystal structures calsequestrin are nearly superimposable not only their subunits but also front-to-front-type dimers. binding curves were measured using atomic absorption spectroscopy. This method enables highly accurate measurements even bound to polymerized protein. The complex, with increases correlated...

Abstract Hydroxycinnamoyltransferase (HCT) from sorghum (Sorghum bicolor) participates in an early step of the phenylpropanoid pathway, exchanging coenzyme A (CoA) esterified to p-coumaric acid with shikimic or quinic as intermediates biosynthesis monolignols coniferyl alcohol and sinapyl alcohol. In order elucidate mode action this enzyme, we have determined crystal structures SbHCT its apo-form ternary complex shikimate p-coumaroyl-CoA, which was converted product during soaking. The...

The p21-activated Ser/Thr kinase 1 (PAK1) has an essential role in tumorigenesis and cell survival many cancers, but its regulation is not fully understood. In this study, we showed that response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, translocated the nucleus. Tyrosine phosphorylation relied upon JAK2 activity for protein stability binding Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition...

TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found be upregulated by TFAP2C. observed that or overexpression led...

Abstract People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes long‐term survivors. Extracellular vesicles (EVs) involved radiation‐induced endothelial dysfunction, but their role the early stage vascular inflammation after exposure remains be fully understood. Herein, we demonstrate that cell‐derived EVs containing miRNAs initiate monocyte activation inflammation. In vitro co‐culture vivo experimental data showed can sensitively...

Glioblastoma (GBM) currently has a dismal prognosis. GBM cells that survive radiotherapy contribute to tumor progression and recurrence with metabolic advantages. Here, we show diacylglycerol kinase B (DGKB), regulator of the intracellular concentration (DAG), is significantly downregulated in radioresistant cells. The downregulation DGKB increases DAG accumulation decreases fatty acid oxidation, contributing radioresistance by reducing mitochondrial lipotoxicity. Diacylglycerol...

The cinnamyl alcohol dehydrogenase (CAD) multigene family in planta encodes proteins catalyzing the reductions of various phenylpropenyl aldehyde derivatives a substrate versatile manner, and whose metabolic products are precursors structural lignins, health-related lignans, other metabolites. In Arabidopsis thaliana, two isoforms, AtCAD5 AtCAD4, catalytically most active being viewed as mainly involved formation guaiacyl/syringyl lignins. this study, we determined crystal structures...

Despite the importance of plant lignans and isoflavonoids in human health protection (e.g. for both treatment prevention onset various cancers) as well biology defense functions heartwood development), systematic studies on enzymes involved their biosynthesis have only recently begun. In this investigation, three NADPH-dependent aromatic alcohol reductases were comprehensively studied, namely pinoresinol-lariciresinol reductase (PLR), phenylcoumaran benzylic ether (PCBER), isoflavone (IFR),...

Burkholderia cepacia AC1100 completely degrades 2,4,5-trichlorophenol, in which an FADH(2)-dependent monooxygenase (TftD) and NADH:FAD oxidoreductase (TftC) catalyze the initial steps. TftD oxidizes 2,4,5-trichlorophenol (2,4,5-TCP) to 2,5-dichloro-p-benzoquinone, is chemically reduced 2,5-dichloro-p-hydroquinone (2,5-DiCHQ). Then, latter 5-chloro-2-hydroxy-p-benzoquinone. In those processes, TftC provides all required FADH(2). We have determined crystal structures of dimeric tetrameric at...

Radiotherapy is the most significant non‐surgical cancer treatment, however it restricted by two major problems: radioresistance and normal tissue damage. We focused on radiation‐induced cell damage, are concerned with inflammation as a main limiting factor in radiotherapy. Psoralidin, coumestan derivative isolated from seed of Psoralea corylifolia , has been studied for various biological properties. However, little known regarding its effects IR‐induced pulmonary inflammation. The aim this...

Radioresistance is considered as a main factor restricting efficacy of radiotherapy. However, the exact molecular mechanism radioresistance has not been explained yet. In this study, to elucidate in lung cancer, we compared radiation responses two types non-small cell cancer (NSCLC) cells with different radiosensitivity and identified key molecules conferring radioresistance. radioresistant NSCLC cells, ionizing (IR) led casein kinase 2α (CK2α)- PKC-mediated phosphorylation rpS3 TRAF2,...

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 glioblastoma (GBM) has not been investigated to date. Here we found that irradiated GBM cells, translocated into nucleus was subsequently ubiquitinated by ring finger 138 (RNF138). Ubiquitin-dependent degradation consequently led radioresistance cells. To elucidate apoptotic rpS3, analyzed...

Radioresistance is a main impediment to effective radiotherapy for non-small cell lung cancer (NSCLC). Despite several experimental and clinical studies of resistance radiation, the precise mechanism radioresistance in NSCLC cells tissues still remains unclear. This result could be explained by limitation previous researches such as partial understanding cellular at single molecule level. In this study, we aimed investigate extensive radiation responses radioresistant identify...