12,662 results match your criteria charged residues

Structure and antimicrobial activity of NCR169, a nodule-specific cysteine-rich peptide of Medicago truncatula.

Sci Rep 2021 May 10;11(1):9923. Epub 2021 May 10.

Center for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan.

A model legume, Medicago truncatula, has over 600 nodule-specific cysteine-rich (NCR) peptides required for symbiosis with rhizobia. Among them, NCR169, an essential factor for establishing symbiosis, has four cysteine residues that are indispensable for its function. However, knowledge of NCR169 structure and mechanism of action is still lacking. Read More

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Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics.

Lancet Microbe 2021 May 4;2(5):e210-e218. Epub 2021 Mar 4.

Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: The COVID-19 agent, SARS-CoV-2, is conspecific with SARS-CoV, the causal agent of the severe acute respiratory syndrome epidemic in 2002-03. Although the viruses share a completely homologous repertoire of proteins and use the same cellular entry receptor, their transmission efficiencies and pathogenetic traits differ. We aimed to compare interferon antagonism by SARS-CoV and SARS-CoV-2. Read More

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Characterization of the Structural Determinants of the Ubiquitin-Dependent Proteasomal Degradation of Human Hepatic Tryptophan 2,3-Dioxygenase.

Biochem J 2021 May 7. Epub 2021 May 7.

University of California San Francisco Center for the Health Professions, San Francisco, California, United States.

Human hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2-3 days for total liver protein. Read More

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Voltage-Sensing Domain of the Third Repeat of Human Skeletal Muscle NaV1.4 Channel As a New Target for Spider Gating Modifier Toxins.

Acta Naturae 2021 Jan-Mar;13(1):134-139

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia.

Voltage-gated sodium channels (NaV) have a modular architecture and contain five membrane domains. The central pore domain is responsible for ion conduction and contains a selectivity filter, while the four peripheral voltage-sensing domains (VSD-I/IV) are responsible for activation and rapid inactivation of the channel. "Gating modifier" toxins from arthropod venoms interact with VSDs, influencing the activation and/or inactivation of the channel, and may serve as prototypes of new drugs for the treatment of various channelopathies and pain syndromes. Read More

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Structural studies of hemoglobin from two flightless birds, ostrich and turkey: insights into their differing oxygen-binding properties.

Acta Crystallogr D Struct Biol 2021 May 26;77(Pt 5):690-702. Epub 2021 Apr 26.

Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India.

Crystal structures of hemoglobin (Hb) from two flightless birds, ostrich (Struthio camelus) and turkey (Meleagris gallopova), were determined. The ostrich Hb structure was solved to a resolution of 2.22 Å, whereas two forms of turkey Hb were solved to resolutions of 1. Read More

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ICAM-1 induced rearrangements of capsid and genome prime rhinovirus 14 for activation and uncoating.

Proc Natl Acad Sci U S A 2021 May;118(19)

Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic

Most rhinoviruses, which are the leading cause of the common cold, utilize intercellular adhesion molecule-1 (ICAM-1) as a receptor to infect cells. To release their genomes, rhinoviruses convert to activated particles that contain pores in the capsid, lack minor capsid protein VP4, and have an altered genome organization. The binding of rhinoviruses to ICAM-1 promotes virus activation; however, the molecular details of the process remain unknown. Read More

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Molecular Mechanism of Small-Molecule Inhibitors in Blocking the PD-1/PD-L1 Pathway through PD-L1 Dimerization.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Key Laboratory for Bio-Based Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou 510630, China.

Programmed cell death-1 (PD-1), which is a molecule involved in the inhibitory signal in the immune system and is important due to blocking of the interactions between PD-1 and programmed cell death ligand-1 (PD-L1), has emerged as a promising immunotherapy for treating cancer. In this work, molecular dynamics simulations were performed on complex systems consisting of the PD-L1 dimer with (S)-BMS-200, (R)-BMS-200 and (MOD)-BMS-200 (i.e. Read More

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Identification of PUFA interaction sites on the cardiac potassium channel KCNQ1.

J Gen Physiol 2021 Jun 3;153(6). Epub 2021 May 3.

Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Polyunsaturated fatty acids (PUFAs), but not saturated fatty acids, modulate ion channels such as the cardiac KCNQ1 channel, although the mechanism is not completely understood. Using both simulations and experiments, we find that PUFAs interact directly with the KCNQ1 channel via two different binding sites: one at the voltage sensor and one at the pore. These two amphiphilic binding pockets stabilize the negatively charged PUFA head group by electrostatic interactions with R218, R221, and K316, while the hydrophobic PUFA tail is selectively stabilized by cassettes of hydrophobic residues. Read More

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Analysis of electrostatic coupling throughout the laboratory evolution of a designed retroaldolase.

Protein Sci 2021 May 2. Epub 2021 May 2.

Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.

The roles of local interactions in the laboratory evolution of a highly active, computationally designed retroaldolase (RA) are examined. Partial Order Optimum Likelihood (POOL) is used to identify catalytically important amino acid interactions in several RA95 enzyme variants. The series RA95. Read More

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Improving the Thermostability and Activity of Transaminase From by Charge-Charge Interaction.

Front Chem 2021 14;9:664156. Epub 2021 Apr 14.

School of Biotechnology and Chemical Engineering, NingboTech University, Ningbo, China.

Transaminases that promote the amination of ketones into amines are an emerging class of biocatalysts for preparing a series of drugs and their intermediates. One of the main limitations of ()-selective amine transaminase from (-ATA) is its weak thermostability, with a half-life () of only 6.9 min at 40°C. Read More

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Analysis of Binding Modes of Antigen-Antibody Complexes by Molecular Mechanics Calculation.

J Chem Inf Model 2021 May 3. Epub 2021 May 3.

Graduate School of Pharmaceutical Sciences, Chiba UniversityRINGGOLD, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.

Antibodies are one of the most important protein molecules in biopharmaceutics. Due to the recent advance in technology for producing monoclonal antibodies, many structural data are available on the antigen-antibody complexes. To characterize the molecular interaction in antigen-antibody recognition, we computationally analyzed 500 complex structures by molecular mechanics calculations. Read More

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Novel STAT3 Small-Molecule Inhibitors Identified by Structure-Based Virtual Ligand Screening Incorporating SH2 Domain Flexibility.

Pharmacol Res 2021 Apr 28:105637. Epub 2021 Apr 28.

Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Efforts to develop STAT3 inhibitors have focused on its SH2 domain starting with short phosphotyrosylated peptides based on STAT3 binding motifs, e.g. pYLPQTV within gp130. Read More

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Identification and Amino Acid Analysis of Allergenic Epitopes of a Novel Allergen Paramyosin (Rap v 2) from .

J Agric Food Chem 2021 Apr 30. Epub 2021 Apr 30.

College of Food Science and Engineering, Ocean University of China, No. 5, Yushan Road, Qingdao, Shandong Province 266003, P.R. China.

Besides tropomyosin (TM) that is widely recognized as a major allergen in molluscs, a 99-kDa novel allergen (Rap v 2) was recently found in the sea snail and identified as paramyosin (PM). However, the allergenic epitopes of PM in any molluscs have not been identified yet. In the present study, seven allergenic epitopes of Rap v 2 were identified by immunoinformatics tools, dot-blot inhibition assay, and basophil degranulation assay. Read More

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Ultrashort Peptide Hydrogels Display Antimicrobial Activity and Enhance Angiogenic Growth Factor Release by Dental Pulp Stem/Stromal Cells.

Materials (Basel) 2021 Apr 27;14(9). Epub 2021 Apr 27.

Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Recent studies on peptide hydrogels have shown that ultrashort peptides (<8 amino acids) can self-assemble into hydrogels. Ultrashort peptides can be designed to incorporate antimicrobial motifs, such as positively charged lysine residues, so that the peptides have inherent antimicrobial characteristics. Antimicrobial hydrogels represent a step change in tissue engineering and merit further investigation, particularly in applications where microbial infection could compromise healing. Read More

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Species-Specific Regulation of TRPM2 by PI(4,5)P via the Membrane Interfacial Cavity.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Institute of Physiology, Medical Faculty, RWTH Aachen University Hospital, D52057 Aachen, Germany.

The human apoptosis channel TRPM2 is stimulated by intracellular ADR-ribose and calcium. Recent studies show pronounced species-specific activation mechanisms. Our aim was to analyse the functional effect of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P), commonly referred to as PIP, on different TRPM2 orthologues. Read More

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Conserved Conformational Hierarchy across Functionally Divergent Glycosyltransferases of the GT-B Structural Superfamily as Determined from Microsecond Molecular Dynamics.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN 55455, USA.

It has long been understood that some proteins undergo conformational transitions en route to the Michaelis Complex to allow chemistry. Examination of crystal structures of glycosyltransferase enzymes in the GT-B structural class reveals that the presence of ligand in the active site triggers an open-to-closed conformation transition, necessary for their catalytic functions. Herein, we describe microsecond molecular dynamics simulations of two distantly related glycosyltransferases that are part of the GT-B structural superfamily, HepI and GtfA. Read More

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Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase.

Int J Mol Sci 2021 Apr 11;22(8). Epub 2021 Apr 11.

Centro Nazionale Malattie Rare, Istituto Superiore di Sanità, 00161 Rome, Italy.

Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. Read More

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Current Understanding of the Structure, Stability and Dynamic Properties of Amyloid Fibrils.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Global Center for Medical Engineering and Informatics, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.

Amyloid fibrils are supramolecular protein assemblies represented by a cross-β structure and fibrous morphology, whose structural architecture has been previously investigated. While amyloid fibrils are basically a main-chain-dominated structure consisting of a backbone of hydrogen bonds, side-chain interactions also play an important role in determining their detailed structures and physicochemical properties. In amyloid fibrils comprising short peptide segments, a steric zipper where a pair of β-sheets with side chains interdigitate tightly is found as a fundamental motif. Read More

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Maintenance of the Neuroprotective Function of the Amino Group Blocked Fluorescence-Agmatine.

Neurochem Res 2021 Apr 29. Epub 2021 Apr 29.

Department of Anatomy, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-gu, Seoul, 03722, Korea.

Agmatine, an endogenous derivative of arginine, has been found to be effective in treating idiopathic pain, convulsion, stress-mediated behavior, and attenuate the withdrawal symptoms of drugs like morphine. In the early stages of ischemic brain injury in animals, exogenous agmatine treatment was found to be neuroprotective. Agmatine is also considered as a putative neurotransmitter and is still an experimental drug. Read More

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Pragmatic mAb lead molecule engineering from a developability perspective.

Biotechnol Bioeng 2021 Apr 29. Epub 2021 Apr 29.

Kymab Ltd., Bennet Building, Babraham Research Campus, Cambridge, CB22 3AT.

As the number of antibody drugs being approved and marketed increases, our knowledge of what makes potential drug candidates a successful product has increased tremendously. One of the critical parameters that has become clear in the field is the importance of mAb 'developability'. Efforts are being increasingly focused on simultaneously selecting molecules that exhibit both desirable biological potencies and manufacturability attributes. Read More

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Conformation-specific perturbation of membrane dynamics by structurally distinct oligomers of Alzheimer's amyloid-β peptide.

Phys Chem Chem Phys 2021 Apr;23(16):9686-9694

Centre for Protein Science Design and Engineering, Indian Institute of Science Education and Research (IISER), Mohali 140306, Punjab, India.

The accumulation of toxic soluble oligomers of the amyloid-β peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease. There are mainly two conformationally distinct oligomers, namely, prefibrillar and fibrillar oligomers, that are recognized by conformation-specific antibodies, anti-amyloid oligomer antibody (A11) and anti-amyloid fibrillar antibody (OC), respectively. Previous studies have shown that the interaction of Aβ oligomers with the lipid membrane is one of the key mechanisms of toxicity produced by Aβ oligomers. Read More

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Optimal RNA binding by Egalitarian, a Dynein cargo adaptor, is critical for maintaining oocyte fate in .

RNA Biol 2021 Apr 27:1-14. Epub 2021 Apr 27.

Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA.

The Dynein motor is responsible for the localization of numerous mRNAs within oocytes and embryos. The RNA binding protein, Egalitarian (Egl), is thought to link these various RNA cargoes with Dynein. Although numerous studies have shown that Egl is able to specifically associate with these RNAs, the nature of these interactions has remained elusive. Read More

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Enzyme kinetic and binding studies identify determinants of specificity for the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease.

Comput Struct Biotechnol J 2021 17;19:2356-2365. Epub 2021 Apr 17.

Department of Biological Sciences, University of Limerick, Limerick, Ireland.

The Streptococcal C5a peptidase (ScpA) specifically inactivates the human complement factor hC5a, a potent anaphylatoxin recently identified as a therapeutic target for treatment of COVID-19 infections. Biologics used to modulate hC5a are predominantly monoclonal antibodies. Here we present data to support an alternative therapeutic approach based on the specific inactivation of hC5a by ScpA in studies using recombinant hC5a (rhC5a). Read More

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A pH-dependent protein stability switch coupled to the perturbed pKa of a single ionizable residue.

Biophys Chem 2021 Apr 20;274:106591. Epub 2021 Apr 20.

Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

The contribution of electrostatic interactions in protein stability has not been fully understood. Burial of an ionizable amino acid inside the hydrophobic protein core can affect its ionization equilibrium and shift its pKa differentially in the native (N) and unfolded (U) states of a protein and this coupling between the folding/unfolding cycle and the ionization equilibria of the ionizable residue can substantially influence the protein stability. Here, we studied the coupling of the folding/unfolding cycle with the ionization of a buried ionizable residue in a multi-domain protein, Human Serum Albumin (HSA) using fluorescence spectroscopy. Read More

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The effect of acidic pH on the adsorption and lytic activity of the peptides Polybia-MP1 and its histidine-containing analog in anionic lipid membrane: a biophysical study by molecular dynamics and spectroscopy.

Amino Acids 2021 Apr 22. Epub 2021 Apr 22.

Department of Physics, IBILCE, UNESP-São Paulo State University, Cristóvão Colombo, 2265-Jardim Nazareth, São José do Rio Preto, SP, 15054-000, Brazil.

Antimicrobial peptides (AMPs) are part of the innate immune system of many species. AMPs are short sequences rich in charged and non-polar residues. They act on the lipid phase of the plasma membrane without requiring membrane receptors. Read More

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Gasdermin D pore structure reveals preferential release of mature interleukin-1.

Nature 2021 Apr 21. Epub 2021 Apr 21.

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.

As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as IL-1β and IL-18. Cleaved GSDMD forms transmembrane pores to enable the release of IL-1 and to drive cell lysis through pyroptosis. Read More

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Residue analytical method for the determination of trifluoroacetic acid and difluoroacetic acid in plant matrices by capillary electrophoresis tandem mass spectrometry (CE-MS/MS).

J Chromatogr A 2021 Jun 22;1646:462096. Epub 2021 Mar 22.

Sciex, Darmstadt, Germany; Horváth Csaba Memorial Laboratory, University of Pannonia, Veszprém, Hungary. Electronic address:

In the past years, the technology for trace residue analysis of plant protection compounds in plant and animal matrices, soil, and water has gradually changed to meet changing regulatory demands. Generally, from the '70s to the '90s of the last century, the active compounds and only a few major metabolites had to be determined in a typical "residue definition". Step by step and within the framework of product safety assessments of the enforcement of residues in dietary matrices and in the environment, further metabolites have come into the authorities focus. Read More

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Uncovering Differences in Hydration Free Energies and Structures for Model Compound Mimics of Charged Side Chains of Amino Acids.

J Phys Chem B 2021 Apr 20;125(16):4148-4161. Epub 2021 Apr 20.

Department of Biomedical Engineering and Center for Science & Engineering of Living Systems, Washington University in St. Louis, St. Louis, Missouri 63130, United States.

Free energies of hydration are of fundamental interest for modeling and understanding conformational and phase equilibria of macromolecular solutes in aqueous phases. Of particular relevance to systems such as intrinsically disordered proteins are the free energies of hydration and hydration structures of model compounds that mimic charged side chains of Arg, Lys, Asp, and Glu. Here, we deploy a Thermodynamic Cycle-based Proton Dissociation (TCPD) approach in conjunction with data from direct measurements to obtain estimates for the free energies of hydration for model compounds that mimic the side chains of Arg, Lys, Asp, and Glu. Read More

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Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Vollum Institute, Oregon Health and Science University, Portland, OR 97239

Myristoylation is a posttranslational modification that plays diverse functional roles in many protein species. The myristate moiety is considered insufficient for protein-membrane associations unless additional membrane-affinity motifs, such as a stretch of positively charged residues, are present. Here, we report that the electrically neutral N-terminal fragment of the protein kinase A catalytic subunit (PKA-C), in which myristoylation is the only functional motif, is sufficient for membrane association. Read More

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Connexin 46 and connexin 50 gap junction channel properties are shaped by structural and dynamic features of their N-terminal domains.

J Physiol 2021 Apr 20. Epub 2021 Apr 20.

Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.

Key Points: Gap junctions formed by different connexins are expressed throughout the body and harbor unique channel properties that have not been fully defined mechanistically. Recent structural studies by Cryo-EM have produced high-resolution models of the related but functionally distinct lens connexins (Cx50 and Cx46) captured in a stable open state, opening the door for structure-function comparison. Here, we conducted comparative MD simulation and electrophysiology studies to dissect the isoform-specific differences in Cx46 and Cx50 intercellular channel function. Read More

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