245,432 results match your criteria binding domain

Identification of novel drug resistance mechanisms by genomic and transcriptomic profiling of glioblastoma cells with mutation-activated EGFR.

Life Sci 2021 May 12:119601. Epub 2021 May 12.

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany. Electronic address:

Aims: Epidermal growth factor receptor (EGFR) is not only involved in carcinogenesis, but also in chemoresistance. We characterized U87.MGΔEGFR glioblastoma cells with constitutively active EGFR due to deletion at the ligand binding domain in terms of gene expression profiling and chromosomal aberrations. Read More

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The binding of different model membranes with PKCε C2 domain is not dependent on membrane curvature but affects the sequence of events during unfolding.

Arch Biochem Biophys 2021 May 12:108910. Epub 2021 May 12.

Departamento de Bioquímica y Biología Molecular (A), Facultad de Veterinaria, International Campus of Excellence Mare Nostrum, Universidad de Murcia, Apartado. 4021, E-30100, Murcia, Spain.

The C2 domain of novel protein kinases C (nPKC) binds to membranes in a Ca-independent way contributing to the activation of these enzymes. We have studied the C2 domain of one of these nPKCs, namely PKCε, and confirmed that it establishes a strong interaction with POPA, which is clearly visible through changes in chemical shifts detected through P-MAS-NMR and the protection that it exerts on the domain against thermal denaturation seen through DSC and FT-IR. In this study, using two-dimensional correlation analysis (2D-COS) applied to infrared spectra, we determined the sequence of events that occur during the thermal unfolding of the domain and highlighted some differences when phosphatidic acid or cardiolipin are present. Read More

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RIPK1/RIPK3-Mediated Necroptosis is Involved in Sevoflurane-Induced Neonatal Neurotoxicity in the Rat Hippocampus.

Cell Mol Neurobiol 2021 May 15. Epub 2021 May 15.

Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital, Fudan University, Fenyang Road #83, Shanghai, 200031, People's Republic of China.

Recent studies have shown that exposure to sevoflurane in developing brains causes neuronal apoptosis and cognitive dysfunction. "Necroptosis" is a novel pathway of necrosis. We introduced the caspase-specific inhibitor Z-VAD in addition to the receptor-interacting protein kinase 1 (RIPK1) inhibitor Nec-1, to ascertain the existence and importance of necroptosis. Read More

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Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity.

Nat Commun 2021 May 14;12(1):2792. Epub 2021 May 14.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain. Read More

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Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions.

Nat Commun 2021 May 14;12(1):2843. Epub 2021 May 14.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although the accessory proteins are considered non-essential for coronavirus replication, accumulating evidences demonstrate they are critical to virus-host interaction and pathogenesis. Orf9b is a unique accessory protein of SARS-CoV-2 and SARS-CoV. It is implicated in immune evasion by targeting mitochondria, where it associates with the versatile adapter TOM70. Read More

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Mol Pharmacol 2021 May 14. Epub 2021 May 14.

Drug Design and Pharmacology, University of Copenhagen, Faculty of Pharmaceutical Sciences, Denmark

Delta selective compound 2 (DS2) is one of the most widely used tools to study selective actions mediated by δ subunit-containing GABA receptors. DS2 was discovered over 10 years ago, but despite great efforts, the precise molecular site of action has remained elusive. Using a combination of computational modeling, site-directed mutagenesis and cell-based pharmacological assays, we probed three potential binding sites for DS2 and analogs at βδ receptors: an αδ interface site in the extracellular domain (ECD), equivalent to the diazepam binding site in αβ receptors, and two sites in the transmembrane domain (TMD); one in the αβ and one in the αβ interface, with the αβ site corresponding to the binding site for etomidate and a recently disclosed low-affinity binding site for diazepam. Read More

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Chromatographic and adsorptive behavior of a bivalent bispecific antibody and associated fragments.

J Chromatogr A 2021 Apr 27;1648:462181. Epub 2021 Apr 27.

Department of Chemical Engineering, University of Virginia, Charlottesville, VA, USA. Electronic address:

The elution and adsorptive behavior of a bivalent bispecific antibody (BiSAb), comprising an IgG1 framework with a scFv domain genetically fused to each heavy chain C-terminus via flexible linkers, and of two associated fragments were studied on two cation exchange chromatography media - ProPac WCX-10, which is pellicular and suitable for analytical use, and Nuvia HR-S, which is macroporous and suitable for preparative and process scale uses. Both fragments were identified by MS as missing one of the two scFv domains and its flexible linker, but one of them also contains an additional C-terminal lysine. The separation of these fragments on both resins occurs as a result of differences in non-specific ligand-protein interactions that are modulated by the salt concentration. Read More

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Structural basis of KdpD histidine kinase binding to the second messenger c-di-AMP.

J Biol Chem 2021 May 11:100771. Epub 2021 May 11.

Department of Medical and Molecular Sciences, 15 Innovation Way, University of Delaware, Newark, DE 19711. Electronic address:

The KdpDE two-component system (TCS) regulates potassium homeostasis and virulence in various bacterial species. The KdpD histidine kinases of this system contain a universal stress protein (USP) domain which binds to the second messenger cyclic-di-adenosine monophosphate (c-di-AMP) for regulating transcriptional output from this TCS in Firmicutes such as Staphylococcus aureus. However, the structural basis of c-di-AMP specificity within the KdpD-USP domain is not well understood. Read More

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Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1.

J Biol Chem 2021 May 11:100772. Epub 2021 May 11.

Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC) - CONICET and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina. Electronic address:

TRIM7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1, the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis, and thus represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal tripartite motif (TRIM) and a variable C-terminal domain. Read More

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Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway.

Curr Biol 2021 May 8. Epub 2021 May 8.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA. Electronic address:

The primary cilium is an essential organizing center for signal transduction, and ciliary defects cause congenital disorders known collectively as ciliopathies. Primary cilia form by two pathways that are employed in a cell-type- and tissue-specific manner: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium first forms inside the cell. After exposure to the external environment, cilia formed via the intracellular pathway may have distinct functional properties, as they often remain recessed within a ciliary pocket. Read More

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Inter-domain horizontal gene transfer of nickel-binding superoxide dismutase.

Geobiology 2021 May 14. Epub 2021 May 14.

Department of Earth and Planetary Science, Harvard University, Cambridge, MA, USA.

The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non-homologous enzymes that perform the same function. Read More

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New approaches to targeting the androgen receptor pathway in prostate cancer.

Clin Adv Hematol Oncol 2021 Apr;19(4):228-240

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.

The androgen signaling axis has been the main therapeutic target in the management of advanced prostate cancer for several decades. Over the past years, significant advances have been made in terms of a better understanding the androgen receptor (AR) pathway and mechanisms of castration resistance, along with the development of more potent AR-targeted therapies. New drugs, such as abiraterone, enzalutamide, apalutamide, and darolutamide, have been approved for castration-resistant prostate cancer and also have demonstrated an overall survival benefit in the castration-sensitive state. Read More

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Non-Native Peptides Capable of Pan-Activating the Quorum Sensing System across Multiple Specificity Groups of .

ACS Chem Biol 2021 May 14. Epub 2021 May 14.

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.

is a leading cause of hospital-acquired infections. Traditional antibiotics have significantly reduced efficacy against this pathogen due to its ability to form biofilms on abiotic surfaces and drug resistance. The accessory gene regulator () quorum sensing system is directly involved in pathogenesis. Read More

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Flexible Loop in Carbohydrate-Binding Module 48 Allosterically Modulates Substrate Binding of the 1,4-α-Glucan Branching Enzyme.

J Agric Food Chem 2021 May 14. Epub 2021 May 14.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China.

The 1,4-α-glucan branching enzyme (GBE, EC 2.4.1. Read More

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TMT-labeled quantitative proteomic analysis to identify proteins associated with the stability of peanut milk.

J Sci Food Agric 2021 May 14. Epub 2021 May 14.

Institute of Agricultural and Sideline Products Processing, Henan Academy of Agricultural Sciences, Zhengzhou, 450002, China.

Background: Peanut milk benefits human health mainly due to its high protein content and suitable amino acid composition. To reveal the molecular mechanism affecting the quality of peanut milk, tandem mass tag (TMT)-labeled proteomic analysis was applied to identify the proteome variation between two peanut cultivars that produced peanut milk with the best and worst stability.

Results: A total of 478 differentially abundant proteins (fold change>1. Read More

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cDNA cloning, expression, and antifungal activity of chitinase from Ficus microcarpa latex: difference in antifungal action of chitinase with and without chitin-binding domain.

Planta 2021 May 13;253(6):120. Epub 2021 May 13.

Department of Bioscience and Biotechnology, University of the Ryukyus, Okinawa, 903-0213, Japan.

Main Conclusion: A chitin-binding domain could contribute to the antifungal ability of chitinase through its affinity to the fungal lateral wall by hydrophobic interactions. Complementary DNA encoding the antifungal chitinase of gazyumaru (Ficus microcarpa), designated GlxChiB, was cloned and expressed in Escherichia coli cells. The results of cDNA cloning showed that the precursor of GlxChiB has an N-terminal endoplasmic reticulum targeting signal and C-terminal vacuolar targeting signal, whereas mature GlxChiB is composed of an N-terminal carbohydrate-binding module family-18 domain (CBM18) and a C-terminal glycoside hydrolase family-19 domain (GH19) with a short linker. Read More

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Transcription factor allosteric regulation through substrate coordination to zinc.

NAR Genom Bioinform 2021 Jun 3;3(2):lqab033. Epub 2021 May 3.

CNC-Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3004-504 Coimbra, Portugal.

The development of new synthetic biology circuits for biotechnology and medicine requires deeper mechanistic insight into allosteric transcription factors (aTFs). Here we studied the aTF UxuR, a homodimer of two domains connected by a highly flexible linker region. To explore how ligand binding to UxuR affects protein dynamics we performed molecular dynamics simulations in the free protein, the aTF bound to the inducer D-fructuronate or the structural isomer D-glucuronate. Read More

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Global alternative splicing landscape of skeletal muscle atrophy induced by hindlimb unloading.

Ann Transl Med 2021 Apr;9(8):643

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Background: Long-term exposure to microgravity will cause skeletal muscle atrophy, which can cause serious harm to astronauts in space travel. Therefore, it is important to explore skeletal muscle atrophy's molecular mechanism for its prevention and treatment. However, as an important regulatory approach of skeletal muscle physiology, the role of alternative splicing in skeletal muscle atrophy, especially skeletal muscle atrophy caused by disuse, is unclear. Read More

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Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion.

Front Mol Biosci 2021 12;8:655662. Epub 2021 Apr 12.

State Key Laboratory of Nonlinear Mechanics (LNM) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.

Cell-cell adhesion and the adhesion of cells to extracellular matrix are mediated by the specific binding of receptors on the cell membrane to their cognate ligands on the opposing surface. The adhesion receptors can exhibit affinity for nanoscale lipid clusters that form in the cell membrane. Experimental studies of such adhesion systems often involve a cell adhering either to a solid surface with immobile ligands or a supported lipid bilayer with mobile ligands. Read More

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Downregulation of SOX9 suppresses breast cancer cell proliferation and migration by regulating apoptosis and cell cycle arrest.

Oncol Lett 2021 Jul 6;22(1):517. Epub 2021 May 6.

Department of Oncology, Tumor Hospital of Gansu Province, Lanzhou, Gansu 730050, P.R. China.

SRY-related high-mobility group box 9 (SOX9) is an important transcriptional factor that regulates diverse genes involved in development and stemness. Dysregulation of SOX9 encourages carcinogenesis in various types of cancer, including breast cancer. The present study aimed to explore the role of SOX9 in triple-negative breast cancer (TNBC). Read More

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Autoantibodies Against the Complement Regulator Factor H in the Serum of Patients With Neuromyelitis Optica Spectrum Disorder.

Front Immunol 2021 27;12:660382. Epub 2021 Apr 27.

Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), characterized by pathogenic, complement-activating autoantibodies against the main water channel in the CNS, aquaporin 4 (AQP4). NMOSD is frequently associated with additional autoantibodies and antibody-mediated diseases. Because the alternative pathway amplifies complement activation, our aim was to evaluate the presence of autoantibodies against the alternative pathway C3 convertase, its components C3b and factor B, and the complement regulator factor H (FH) in NMOSD. Read More

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IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.

Nat Microbiol 2021 May 13. Epub 2021 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. Read More

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Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase.

Sci Rep 2021 May 13;11(1):10290. Epub 2021 May 13.

Nazarbayev University School of Medicine, Nazarbayev University, Astana, Kazakhstan.

As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. Read More

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Biochemical and structural insights into Rab12 interactions with RILP and its family members.

Sci Rep 2021 May 13;11(1):10317. Epub 2021 May 13.

Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.

Alongside its biosynthetic functions, the small GTPase Rab12 negatively regulates mast cell (MC) exocytosis by its interaction with RILP to promote retrograde transport of the MC secretory granules. Given the role of Rab effectors in mediating Rab functions, in this study we used biochemical and in silico tools to decipher Rab12 interactions with its RILP family effectors. We show that Rab12 interacts with RILP, RILP-L1 and RILP-L2 independently of each other, whereby lysine-71, in mouse Rab12, is critical for Rab12 interactions with RILP-L1 or RILP-L2, but is dispensable for the binding of RILP. Read More

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lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition.

Oncol Res 2021 May 13. Epub 2021 May 13.

Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China.

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Read More

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Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal.

Mil Med Res 2021 May 13;8(1):30. Epub 2021 May 13.

Department of Respiratory and Critical Care Medicine, Air Force Medical Center of Chinese PLA, Beijing, 100142, China.

Background: Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.

Methods: A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Read More

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Solution structure of the Myb domain of Terfa derived from Zebrafish interacting with both human and plant telomeric DNA.

Biochem Biophys Res Commun 2021 May 10;559:252-258. Epub 2021 May 10.

PCG-Biotech, Ltd., Yonsei Engineering Research Park, Yonsei University, Seoul, 120-749, Republic of Korea; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea. Electronic address:

Telomeric repeat binding factor a (Terfa) derived from zebrafish is a homologous protein with human telomeric repeat binding factor 2 (TRF2). Terfa is known as a senescence-associated biomarker in various research through the zebrafish animal model. In addition, according to the findings so far, it has been confirmed that human or plant telomere binding proteins bind to telomeric DNA specialized for each species, but, in our result, Terfa shows it strongly binds to both human or plant type telomeric DNA. Read More

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Epigenetic Regulation of Melanogenesis.

Ageing Res Rev 2021 May 10:101349. Epub 2021 May 10.

Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, PR China. Electronic address:

Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways. Epigenetics refers to the potential genetic changes that affect gene expression without involving changes in the original sequence of DNA nucleotides. DNA methylation regulates the expression of key genes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT) and microphthalmia-associated transcription factor (MITF), as well as paracrine factors such as stem cell factor (SCF) and endothelin-1 (ET-1) in melanogenesis. Read More

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The binding of LDN193189 to CD133 C-terminus suppresses the tumorigenesis and immune escape of liver tumor-initiating cells.

Cancer Lett 2021 May 10. Epub 2021 May 10.

NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, PR China. Electronic address:

The tumor-initiating cell (TIC) marker CD133 promotes TIC self-renewal and tumorigenesis through the tyrosine phosphorylation of its c-terminal domain. Therefore, finding compounds that target the phosphorylation of CD133 will provide an effective method for inhibiting TICs characteristics. Here, through small molecule microarray screening, compound LDN193189 was found to bind to the c-terminus of CD133 and influenced its tyrosine phosphorylation. Read More

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Molecular simulation studies of the interactions between the human/pangolin/cat/bat ACE2 and the receptor binding domain of the SARS-CoV-2 spike protein.

Biochimie 2021 May 10. Epub 2021 May 10.

Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; Shanghai Institute for Advanced Immunochemical Studies, And School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

The recent outbreak of SARS-CoV-2 has had a profound effect on the world. Similar to that in SARS-CoV, the entry receptor of SARS-CoV-2 is ACE2. The binding of SARS-CoV-2 spike protein to ACE2 is the critical to the virus infection. Read More

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