Structural analysis of the FERM domain of human protein tyrosine phosphatase non-receptor type 21.

Protein tyrosine phosphatase non-receptor type 21 (PTPN21) is a cytosolic protein tyrosine phosphatase that regulates cell growth and invasion. Due to its oncogenic properties, PTPN21 has recently emerged as a potential therapeutic target for cancer. In this study, the three-dimensional structure of the PTPN21 FERM domain was determined at 2.

Insights into the recognition mechanism in the UBR box of UBR4 for its specific substrates.

The N-end rule pathway is a proteolytic system involving the destabilization of N-terminal amino acids, known as N-degrons, which are recognized by N-recognins. Dysregulation of the N-end rule pathway results in the accumulation of undesired proteins, causing various diseases. The E3 ligases of the UBR subfamily recognize and degrade N-degrons through the ubiquitin-proteasome system.

Crystal Structures of Plk1 Polo-Box Domain Bound to the Human Papillomavirus Minor Capsid Protein L2-Derived Peptide.

Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly encode two structural (L1 and L2) and seven functional (E1, E2, E4-E7, and E8) proteins.

Structural and biochemical analysis of the PTPN4 PDZ domain bound to the C-terminal tail of the human papillomavirus E6 oncoprotein.

High-risk genotypes of human papillomaviruses (HPVs) are directly implicated in various abnormalities associated with cellular hyperproliferation, including cervical cancer. E6 is one of two oncoproteins encoded in the HPV genome, which recruits diverse PSD-95/Dlg/ZO-1 (PDZ) domain-containing human proteins through its C-terminal PDZ-binding motif (PBM) to be degraded by means of the proteasome pathway. Among the three PDZ domain-containing protein tyrosine phosphatases, protein tyrosine phosphatase non-receptor type 3 (PTPN3) and PTPN13 were identified to be recognized by HPV E6 in a PBM-dependent manner.

Correlation between occlusal contact area at various levels of interocclusal thicknesses and masticatory performance.

Background: This study aimed to determine the correlation between occlusal contact area and masticatory performance using BiteEye , a photo occlusal analysis device and the multiple sieve method.

Objectives: To calculate the occlusal contact area at various levels of interocclusal thicknesses and to measure masticatory performance with peanuts as the test material.

Methods: Fifty-two adults (30 men and 22 women) were enrolled according to specific exclusion/inclusion criteria.

R-catcher, a potent molecular tool to unveil the arginylome.

Protein arginylation is a critical regulator of a variety of biological processes. The ability to uncover the global arginylation pattern and its associated signaling pathways would enable us to identify novel disease targets. Here, we report the development of a tool able to capture the N-terminal arginylome.

Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18.

Human papillomaviruses (HPVs) cause cellular hyperproliferation-associated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a well-defined tumor suppressor, and found that this intermolecular interaction plays a key role in E7-driven transformation and tumorigenesis.

Structural and Biochemical Characterization of the Two Low Molecular Weight-Protein Tyrosine Phosphatases DARP and Primo-1.

The genome contains four low molecular weightprotein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical analysis has limited our understanding of these proteins. Primo-1 and CG31469 were previously classified as pseudophosphatases, but CG31469 was also suggested to be a putative protein arginine phosphatase.

Clinical Utility of Combined Circulating Tumor Cell and Circulating Tumor DNA Assays for Diagnosis of Primary Lung Cancer.

Background/aim: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination.

Patients And Methods: From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study.

Oligomer Model of PB1 Domain of p62/SQSTM1 Based on Crystal Structure of Homo-Dimer and Calculation of Helical Characteristics.

Autophagy is an important process for protein recycling. Oligomerization of p62/SQSTM1 is an essential step in this process and is achieved in two steps. Phox and Bem1p (PB1) domains can oligomerize through both basic and acidic surfaces in each molecule.

A Novel Application of Buprenorphine Transdermal Patch to Relieve Pain in the Knee Joint of Knee Osteoarthritis Patients: A Retrospective Case-Control Study.

Osteoarthritis (OA) is considered to be one of the most disabling diseases. The intra-articular opioid injection has been widely studied for its simplicity, safety, and efficacy in OA. In this study, however, we suggest a novel method of buprenorphine transdermal patch (BTDP) to painful knee joints of OA patients, instead of intra-articular opioid injection, and subsequently compared the knee application with conventional chest application.

Identification of circulating tumor cells with EML4-ALK translocation using fluorescence hybridization in advanced ALK-positive patients with lung cancer.

[This retracts the article DOI: 10.3892/ol.2018.

Structural and Physiological Exploration of Typhi YfdX Uncovers Its Dual Function in Bacterial Antibiotic Stress and Virulence.

YfdX is a prokaryotic protein encoded by several pathogenic bacteria including serovar Typhi, which causes one of the most fatal infectious diseases, typhoid fever. YfdX is a product of the operon and is known to be under the control of EvgA, a regulator protein controlling the expression of several proteins involved in response to environmental stress, in . Nevertheless, unlike other proteins encoded by the same operon, the structural and physiological aspects of YfdX have been poorly characterized.

Effect of Size and Location of Nevi on Postoperative Pain and Emergence Agitation in Children Undergoing Nevi Excision.

Congenital melanocytic nevi need surgical excisions. However, the effect of the size and location of the nevi on pain and emergence agitation have yet to be studied. The objective of this study was to evaluate (1) the ideal parameter of the nevus size and (2) the effects of the size and location of the nevus on pain and emergence agitation.

Identification of circulating tumor cells with EML4-ALK translocation using fluorescence hybridization in advanced ALK-positive patients with lung cancer.

Analysis of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) is considered to be a useful tool when considering predictive biomarker detection for evaluating eligibility for targeted therapy. It is not always possible to perform a tumor biopsy in patients. Isolation and culturing of circulating tumor cells (CTCs) may be an alternative to tumor biopsies for the diagnosis of ALK rearrangement.

Crystal structures of two forms of the Acanthamoeba polyphaga mimivirus Rab GTPase.

Acanthamoeba polyphaga mimivirus (APMV) is a member of the family of giant viruses, harboring a 1,200 kbp genome within its 700 nm-diameter viral particle. The R214 gene of the APMV genome was recently shown to encode a homologue of the Rab GTPases, molecular switch proteins known to play a pivotal role in the regulation of membrane trafficking that were considered to exist only in eukaryotes. Herein, we report the first crystal structures of GDP- and GTP-bound forms of APMV Rab GTPase, both of which were determined at high resolution.

Two-track virtual screening approach to identify both competitive and allosteric inhibitors of human small C-terminal domain phosphatase 1.

Despite a wealth of persuasive evidence for the involvement of human small C-terminal domain phosphatase 1 (Scp1) in the impairment of neuronal differentiation and in Huntington's disease, small-molecule inhibitors of Scp1 have been rarely reported so far. This study aims to the discovery of both competitive and allosteric Scp1 inhibitors through the two-track virtual screening procedure. By virtue of the improvement of the scoring function by implementing a new molecular solvation energy term and by reoptimizing the atomic charges for the active-site Mg ion cluster, we have been able to identify three allosteric and five competitive Scp1 inhibitors with low-micromolar inhibitory activity.

Cancer gene panel analysis of cultured circulating tumor cells and primary tumor tissue from patients with breast cancer.

Although numerous effective therapies have improved the survival rate of patients with breast cancer, a number of patients present with tumor recurrence and metastasis. A liquid biopsy of circulating tumor cells (CTC) is a non-invasive method to obtain tumor cells and may be used as substitute for a tumor tissue biopsy. The present study focuses on determining whether CTC culture is an optimal method of obtaining sufficient amounts of CTCs for molecular analysis.

Crystal structure of SP-PTP, a low molecular weight protein tyrosine phosphatase from Streptococcus pyogenes.

Streptococcus pyogenes, or Group A Streptococcus (GAS), is a pathogenic bacterium that causes a variety of infectious diseases. The GAS genome encodes one protein tyrosine phosphatase, SP-PTP, which plays an essential role in the replication and virulence maintenance of GAS. Herein, we present the crystal structure of SP-PTP at 1.

Identification of novel protein tyrosine phosphatase sigma inhibitors promoting neurite extension.

Protein tyrosine phosphatase sigma (PTPσ) is a potential target for the therapeutic treatment of neurological deficits associated with impaired neuronal recovery, as this protein is the receptor for chondroitin sulfate proteoglycan (CSPG), which is known to inhibit neuronal regeneration. Through a high-throughput screening approach started from 6400 representative compounds in the Korea Chemical Bank chemical library, we identified 11 novel PTPσ inhibitors that can be classified as flavonoid derivatives or analogs, with IC50 values ranging from 0.5 to 17.

Virtual Screening with Docking Simulations and Biochemical Evaluation of VHY Phosphatase Inhibitors.

Although VH1-related member Y (VHY) phosphatase is responsible for the pathogenesis of neuroinflammatory diseases, no small-molecule inhibitor of VHY has been reported so far. Here we first report eight VHY inhibitors identified from molecular docking-based virtual screening and subsequent enzyme inhibition assays. These inhibitors exhibit good biochemical potencies against VHY, with associated IC50 values ranging from 1 to 9 µM.

Optimization for enhancement of signal effectiveness in three-dimensional (3D) cell based electrochemical biosensor.

This study addresses the optimization for enhancement of signal effectiveness in 3D cell based electrochemical biosensor. While 2D culture has a structural limitation to mimic an in vivo, 3D culture can provide more similar cell responses. In addition, although 3D cultured cells have been applied to measure electrically, the intensity of electrical signal from cells on the electrode was extremely low.