26,077 results match your criteria conformational state


Mechanism of REST/NRSF regulation of clustered protocadherin α genes.

Nucleic Acids Res 2021 Apr 13. Epub 2021 Apr 13.

Center for Comparative Biomedicine, MOE Key Laboratory of Systems Biomedicine, State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.

Repressor element-1 silencing transcription factor (REST) or neuron-restrictive silencer factor (NRSF) is a zinc-finger (ZF) containing transcriptional repressor that recognizes thousands of neuron-restrictive silencer elements (NRSEs) in mammalian genomes. How REST/NRSF regulates gene expression remains incompletely understood. Here, we investigate the binding pattern and regulation mechanism of REST/NRSF in the clustered protocadherin (PCDH) genes. Read More

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Interface-Mediated Mechanism of Action-The Root of the Cytoprotective Effect of Immediate-Release Omeprazole.

J Med Chem 2021 Apr 13. Epub 2021 Apr 13.

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.

Omeprazole is usually administered under an enteric coating. However, there is a Food and Drug Administration-approved strategy that enables its release in the stomach. When locally absorbed, omeprazole shows a higher efficacy and a cytoprotective effect, whose mechanism was still unknown. Read More

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Photocontrolled Nanopipette Biosensor for ATP Gradient Electroanalysis of Single Living Cells.

ACS Sens 2021 Apr 13. Epub 2021 Apr 13.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.

Emerging nanopipette tools have demonstrated substantial potential for advanced single-cell analysis, which plays vital roles from fundamental cellular biology to biomedical diagnostics. Highly recyclable nanopipettes with easy and quick regeneration are of special interest for precise and multiple measurements. However, existing recycle strategies are generally plagued by operational complexity and limited efficiency. Read More

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Molecular Insights into Myocilin and Its Glaucoma-Causing Misfolded Olfactomedin Domain Variants.

Acc Chem Res 2021 Apr 13. Epub 2021 Apr 13.

School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr. NW, Atlanta, Georgia 30332-0400, United States.

ConspectusNumerous human disorders arise due to the inability of a particular protein to adopt its correct three-dimensional structure in the context of the cell, leading to aggregation. A new addition to the list of such protein conformational disorders is the inherited subtype of glaucoma. Different and rare coding mutations in myocilin, found in families throughout the world, are causal for early onset ocular hypertension, a key glaucoma risk factor. Read More

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Potential aggregation hot spots in recombinant human keratinocyte growth factor: a computational study.

J Biomol Struct Dyn 2021 Apr 10:1-16. Epub 2021 Apr 10.

Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.

The recombinant human keratinocyte growth factor (rhKGF) is a highly aggregation-prone therapeutic protein. The high aggregation liability of rhKGF is manifested by loss of the monomeric state, and accumulation of the aggregated species even at moderate temperatures. Here, we analyzed the rhKGF for its vulnerability toward aggregation by detection of aggregation-prone regions (APRs) using several sequence-based computational tools including TANGO, ZipperDB, AGGRESCAN, Zyggregator, Camsol, PASTA, SALSA, WALTZ, SODA, Amylpred, AMYPDB, and structure-based tools including SolubiS, CamSol structurally corrected, Aggrescan3D and spatial aggregation propensity (SAP) algorithm. Read More

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Molecular Basis of Class B GPCR Selectivity for the Neuropeptides PACAP and VIP.

Front Mol Biosci 2021 25;8:644644. Epub 2021 Mar 25.

Department of Chemistry, University of Vermont, Burlington, VT, United States.

The related neuropeptides PACAP and VIP, and their shared PAC1, VPAC1 and VPAC2 receptors, regulate a large array of physiological activities in the central and peripheral nervous systems. However, the lack of comparative and molecular mechanistic investigations hinder further understanding of their preferred binding selectivity and function. PACAP and VIP have comparable affinity at the VPAC1 and VPAC2 receptor, but PACAP is 400-1,000 fold more potent than VIP at the PAC1 receptor. Read More

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The Enigma of Substrate Recognition and Catalytic Efficiency of APE1-Like Enzymes.

Front Cell Dev Biol 2021 26;9:617161. Epub 2021 Mar 26.

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.

Despite significant achievements in the elucidation of the nature of protein-DNA contacts that control the specificity of nucleotide incision repair (NIR) by apurinic/apyrimidinic (AP) endonucleases, the question on how a given nucleotide is accommodated by the active site of the enzyme remains unanswered. Therefore, the main purpose of our study was to compare kinetics of conformational changes of three homologous APE1-like endonucleases (insect Rrp1, amphibian xAPE1, and fish zAPE1) during their interaction with various damaged DNA substrates, i.e. Read More

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Thiazole-amino acids: influence of thiazole ring on conformational properties of amino acid residues.

Amino Acids 2021 Apr 10. Epub 2021 Apr 10.

Faculty of Chemistry, University of Opole, 45-052, Opole, Poland.

Post-translational modified thiazole-amino acid (Xaa-Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Read More

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Developments in solution-state NMR yield broader and deeper views of the dynamic ensembles of nucleic acids.

Curr Opin Struct Biol 2021 Apr 6;70:16-25. Epub 2021 Apr 6.

Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA; Department of Chemistry, Duke University, Durham, NC, USA. Electronic address:

Nucleic acids do not fold into a single conformation, and dynamic ensembles are needed to describe their propensities to cycle between different conformations when performing cellular functions. We review recent advances in solution-state nuclear magnetic resonance (NMR) methods and their integration with computational techniques that are improving the ability to probe the dynamic ensembles of DNA and RNA. These include computational approaches for predicting chemical shifts from structure and generating conformational libraries from sequence, measurements of exact nuclear Overhauser effects, development of new probes to study chemical exchange using relaxation dispersion, faster and more sensitive real-time NMR techniques, and new NMR approaches to tackle large nucleic acid assemblies. Read More

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How do antiporters exchange substrates across the cell membrane? An atomic-level description of the complete exchange cycle in NarK.

Structure 2021 Apr 2. Epub 2021 Apr 2.

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Plant Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; NIH Center for Macromolecular Modeling and Bioinformatics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Digital Agriculture, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address:

Major facilitator superfamily (MFS) proteins operate via three different mechanisms: uniport, symport, and antiport. Despite extensive investigations, the molecular understanding of antiporters is less advanced than that of other transporters due to the complex coupling between two substrates and the lack of distinct structures. We employ extensive all-atom molecular dynamics simulations to dissect the complete substrate exchange cycle of the bacterial NO/NO antiporter, NarK. Read More

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Machine learning of free energies in chemical compound space using ensemble representations: Reaching experimental uncertainty for solvation.

J Chem Phys 2021 Apr;154(13):134113

University of Vienna, Faculty of Physics, Kolingasse 14-16, AT-1090 Wien, Austria.

Free energies govern the behavior of soft and liquid matter, and improving their predictions could have a large impact on the development of drugs, electrolytes, or homogeneous catalysts. Unfortunately, it is challenging to devise an accurate description of effects governing solvation such as hydrogen-bonding, van der Waals interactions, or conformational sampling. We present a Free energy Machine Learning (FML) model applicable throughout chemical compound space and based on a representation that employs Boltzmann averages to account for an approximated sampling of configurational space. Read More

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Toggle switch residues control allosteric transitions in bacterial adhesins by participating in a concerted repacking of the protein core.

PLoS Pathog 2021 Apr 7;17(4):e1009440. Epub 2021 Apr 7.

Department of Microbiology, University of Washington, Seattle, Washington, United States of America.

Critical molecular events that control conformational transitions in most allosteric proteins are ill-defined. The mannose-specific FimH protein of Escherichia coli is a prototypic bacterial adhesin that switches from an 'inactive' low-affinity state (LAS) to an 'active' high-affinity state (HAS) conformation allosterically upon mannose binding and mediates shear-dependent catch bond adhesion. Here we identify a novel type of antibody that acts as a kinetic trap and prevents the transition between conformations in both directions. Read More

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Engineering Protease-Resistant Peptides to Inhibit Human Parainfluenza Viral Respiratory Infection.

J Am Chem Soc 2021 Apr 7. Epub 2021 Apr 7.

Department of Pediatrics, Columbia University Vagelos College of Physicians & Surgeons, New York, New York 10032, United States.

The lower respiratory tract infections affecting children worldwide are in large part caused by the parainfluenza viruses (HPIVs), particularly HPIV3, along with human metapneumovirus and respiratory syncytial virus, enveloped negative-strand RNA viruses. There are no vaccines for these important human pathogens, and existing treatments have limited or no efficacy. Infection by HPIV is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Read More

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