Structural study for substrate recognition of human N-terminal glutamine amidohydrolase 1 in the arginine N-degron pathway.

The N-degron pathway determines the half-life of proteins by selectively destabilizing the proteins bearing N-degrons. N-terminal glutamine amidohydrolase 1 (NTAQ1) plays an essential role in the arginine N-degron (Arg/N-degron) pathway as an initializing enzyme via the deamidation of the N-terminal (Nt) glutamine (Gln). However, the Nt-serine-bound conformation of hNTAQ1 according to the previously identified crystal structure suggests the possibility of other factors influencing the recognition of Nt residues by hNTAQ1.

Sludge-based candidate reference materials for enhanced quality control of particulate processes in total organic carbon analysis for wastewater.

Accurate analyses of total organic carbon (TOC) encompassing particulate organic carbon in wastewater are key for evaluating the behavior of particulate organic contaminants and maintaining the carbon mass balance throughout the wastewater treatment process. This study was conducted to develop candidate reference materials of environmental origin from excess sludge collected from wastewater treatment facilities, primarily receiving industrial wastewater and livestock manure as the main sources. Homogeneity and stability assessments for total carbon (TC) and TOC were conducted in the particle samples following the standardized procedures of ISO Guide 35 and ISO 13258.

A Case Report for Myopericarditis after BNT162b2 COVID-19 mRNA Vaccination in a Korean Young Male.

Mass vaccination with the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine (BNT162b2) in Korea has resulted in many reported adverse effects. These side effects are the object of much scrutiny in the medical community. We report the case of a 29-year-old male who was diagnosed with myopericarditis after his second dose of Pfizer-BioNTech COVID-19 vaccine.

Differential Effects of Cancer-Associated Mutations Enriched in Helix H3 of PPARγ.

Peroxisome proliferator-activated receptor gamma (PPARγ) has recently been revealed to regulate tumor microenvironments. In particular, genetic alterations of PPARγ found in various cancers have been reported to play important roles in tumorigenesis by affecting PPARγ transactivation. In this study, we found that helix H3 of the PPARγ ligand-binding domain (LBD) has a number of sites that are mutated in cancers.

Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein.

The N-Myc downstream-regulated gene (NDRG) family belongs to the α/β-hydrolase fold and is known to exert various physiologic functions in cell proliferation, differentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear.

Structural and Functional Analyses of Human ChaC2 in Glutathione Metabolism.

Glutathione (GSH) degradation plays an essential role in GSH homeostasis, which regulates cell survival, especially in cancer cells. Among human GSH degradation enzymes, the ChaC2 enzyme acts on GSH to form 5-l-oxoproline and Cys-Gly specifically in the cytosol. Here, we report the crystal structures of ChaC2 in two different conformations and compare the structural features with other known γ-glutamylcyclotransferase enzymes.

Publisher Correction: Structural basis for the inhibitory effects of a novel reversible covalent ligand on PPARγ phosphorylation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Structural Basis for the Regulation of PPARγ Activity by Imatinib.

Imatinib is an effective anticancer drug for the treatment of leukemia. Interestingly, when an FDA-approved drug library was tested for agents that block peroxisome proliferator-activated receptor γ (PPARγ) phosphorylation at Ser245 to evaluate possibilities of antidiabetic drug repositioning, imatinib was determined as a PPARγ antagonist ligand. However, it is not well understood how imatinib binds to PPARγ or would improve insulin sensitivity without classical agonism.

Structural basis for the inhibitory effects of a novel reversible covalent ligand on PPARγ phosphorylation.

Peroxisome proliferator-activated receptor γ (PPARγ) is a major therapeutic target for the treatment of type 2 diabetes. However, the use of PPARγ-targeted drugs, such as rosiglitazone and pioglitazone, is limited owing to serious side effects caused by classical agonism. Using a rational drug discovery approach, we recently developed SB1495, a novel reversible covalent inhibitor of the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of PPARγ at Ser245, a key factor in the insulin-sensitizing effect of PPARγ-targeted drugs.

Early Quantitative Partial Weight-Bearing Exercise After Periarticular Fractures of the Tibia Using a Lower-Body Positive-Pressure Treadmill: A Case Series.

The partial weight-bearing protocol after lower limb fracture is an important issue in postoperative rehabilitation. Because it is difficult to quantify the actual weight load and provide a constant weight, the protocol is unestablished. By training with a lower-body positive-pressure treadmill and using an in-shoe pressure-measuring device, partial weight-bearing exercise can be performed with quantified loads.

Development and validation of the Korean version of the medication regimen complexity index.

The medication regimen complexity index (MRCI), originally developed in English, is a reliable and valid tool to assess the complexity of pharmacotherapy. This study aimed to validate the Korean version of MRCI (MRCI-K). A cross-cultural methodological study comprising 335 discharged patients of a tertiary hospital in Korea was conducted.

The Fungal Metabolite Eurochevalierine, a Sequiterpene Alkaloid, Displays Anti-Cancer Properties through Selective Sirtuin 1/2 Inhibition.

NAD⁺-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has been of significant interest for diverse therapeutic applications. In particular, it has been shown that inhibition of sirtuin 1 and 2 activities is beneficial for cancer treatment.

Structural Basis for the Enhanced Anti-Diabetic Efficacy of Lobeglitazone on PPARγ.

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, insulin resistance, and inflammation. Here, we report the crystal structures of PPARγ in complex with lobeglitazone, a novel PPARγ agonist, and with rosiglitazone for comparison.

Discovery and Characterization of R/S-N-3-Cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea, a New Histone Deacetylase Class III Inhibitor Exerting Antiproliferative Activity against Cancer Cell Lines.

A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea] which displays a potent antiproliferative activity on various glioma cell types, assessed by quantitative videomicroscopy, eventually triggering senescence. The impact on normal glial cells was lower with a selectivity index of >10.

Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternate site.

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPARγ agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.

Structural Basis of the Heterodimer Formation between Cell Shape-Determining Proteins Csd1 and Csd2 from Helicobacter pylori.

Colonization of the human gastric mucosa by Helicobacter pylori requires its high motility, which depends on the helical cell shape. In H. pylori, several genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5, and csd6) play key roles in determining the cell shape by alteration of cross-linking or by trimming of peptidoglycan stem peptides.

Mechanistic elucidation guided by covalent inhibitors for the development of anti-diabetic PPARγ ligands.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-regulated transcription factor that plays crucial roles in adipogenesis, lipid metabolism, and glucose homeostasis. Several PPARγ ligands possess anti-diabetic activity and they commonly inhibit the phosphorylation of PPARγ at serine 273 (Ser273). The recently reported PPARγ ligand SR1664, which selectively blocks the phosphorylation of PPARγ without classical agonism, has potent anti-diabetic activity, indicating that the inhibition of Ser273 phosphorylation is sufficient to provoke anti-diabetic effects.

Deep-Plane Lipoabdominoplasty in East Asians.

Background: The objective of this study was to develop a new surgical technique by combining traditional abdominoplasty with liposuction. This combination of operations permits simpler and more accurate management of various abdominal deformities. In lipoabdominoplasty, the combination of techniques is of paramount concern.

Crystal structure of Rv2258c from Mycobacterium tuberculosis H37Rv, an S-adenosyl-l-methionine-dependent methyltransferase.

The Mycobacterium tuberculosis Rv2258c protein is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase). Here, we have determined its crystal structure in three forms: a ligand-unbound form, a binary complex with sinefungin (SFG), and a binary complex with S-adenosyl-L-homocysteine (SAH). The monomer structure of Rv2258c consists of two domains which are linked by a long α-helix.

The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase.

Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H.

Structure of Csd3 from Helicobacter pylori, a cell shape-determining metallopeptidase.

Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H.

Fullerene embedded shape memory nanolens array.

Securing fragile nanostructures against external impact is indispensable for offering sufficiently long lifetime in service to nanoengineering products, especially when coming in contact with other substances. Indeed, this problem still remains a challenging task, which may be resolved with the help of smart materials such as shape memory and self-healing materials. Here, we demonstrate a shape memory nanostructure that can recover its shape by absorbing electromagnetic energy.

High-resolution crystal structure of Streptococcus pyogenes β-NAD⁺ glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface.

One of the virulence factors produced by Streptococcus pyogenes is β-NAD(+) glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway.

Crystal structures of Pseudomonas aeruginosa guanidinobutyrase and guanidinopropionase, members of the ureohydrolase superfamily.

Pseudomonas aeruginosa guanidinobutyrase (GbuA) and guanidinopropionase (GpuA) catalyze the hydrolysis of 4-guanidinobutyrate and 3-guanidinopropionate, respectively. They belong to the ureohydrolase superfamily, which includes arginase, agmatinase, proclavaminate amidinohydrolase, and formiminoglutamase. In this study, we have determined the crystal structures of GbuA and GpuA from P.

Helicobacter pylori proinflammatory protein up-regulates NF-kappaB as a cell-translocating Ser/Thr kinase.

There has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages.