18,136 results match your criteria backbone conformation

Aspartic protease-pepstatin A interactions: Structural insights on the thermal inactivation mechanism.

Biochimie 2021 Jun 8. Epub 2021 Jun 8.

Kaypeeyes Biotech Private Limited, R&D Center, Hebbal Industrial Area, Mysuru, 570016, Karnataka, India. Electronic address:

Aspartic proteases are the targets for structure-based drug design for their role in physiological processes and pharmaceutical applications. Structural insights into the thermal inactivation mechanism of an aspartic protease in presence and absence of bound pepstatin A have been obtained by kinetics of thermal inactivation, CD, fluorescence spectroscopy and molecular dynamic simulations. The irreversible thermal inactivation of the aspartic protease comprised of loss of tertiary and secondary structures succeeded by the loss of activity, autolysis and aggregation The enthalpy and entropy of thermal inactivation of the enzyme in presence of pepstatin A increased from 81. Read More

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Longer charged amino acids favor β-strand formation in hairpin peptides.

J Pept Sci 2021 Jun 10:e3333. Epub 2021 Jun 10.

Department of Chemistry, National Taiwan University, Taipei, Taiwan.

Interactions between charged amino acids significantly influence the structure and function of proteins. The encoded charged amino acids Asp, Glu, Arg, and Lys have different number of hydrophobic methylenes linking the backbone to the charged functionality. It remains to be fully understood how does this difference in the number of methylenes affect protein structure stability. Read More

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Crystal structure of Z-DNA in complex with the polyamine putrescine and potassium cations at ultra-high resolution.

Acta Crystallogr B Struct Sci Cryst Eng Mater 2021 Jun 6;77(Pt 3):331-338. Epub 2021 May 6.

Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.

The X-ray crystal structure of the d(CGCGCG)/putrescine(2+)/K complex has been determined at 0.60 Å resolution. Stereochemical restraints were used only for the putrescinium dication, and 23 bonds and 18 angles of the Z-DNA nucleotides with dual conformation. Read More

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Increasing protein stability by engineering the n → π* interaction at the β-turn.

Chem Sci 2020 Jul 30;11(35):9480-9487. Epub 2020 Jul 30.

Molecular Biophysics Unit, Indian Institute of Science Bangalore 560012 India

Abundant n → π* interactions between adjacent backbone carbonyl groups, identified by statistical analysis of protein structures, are predicted to play an important role in dictating the structure of proteins. However, experimentally testing the prediction in proteins has been challenging due to the weak nature of this interaction. By amplifying the strength of the n → π* interaction amino acid substitution and thioamide incorporation at a solvent exposed β-turn within the proteins and Pin 1 WW domain, we demonstrate that an n → π* interaction increases the structural stability of proteins by restricting the torsion angle. Read More

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An 8-Hydroxy-Quinoline Derivative Protects Against Lipopolysaccharide-Induced Lethality in Endotoxemia by Inhibiting HMGB1-Mediated Caspase-11 Signaling.

Front Pharmacol 2021 21;12:673818. Epub 2021 May 21.

Department of Physiology, School of Basic Medical Science, Central South University, Changsha, China.

Sepsis, an inflammatory syndrome secondary to infection, is the leading cause of in-hospital lethality. It is evidenced that LPS, the major pathological component of the Gram-negative bacteria membrane, predominantly contributes to the pathogenesis of sepsis. Cytoplasmic lipopolysaccharide (LPS) can be sensed by the noncanonical inflammasome and triggers the oligomerization of caspase-11, resulting in pyroptosis and lethal immune responses in sepsis. Read More

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Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity.

PLoS Biol 2021 Jun 4;19(6):e3001295. Epub 2021 Jun 4.

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. Read More

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A Machine-Learning Protocol for Ultraviolet Protein-Backbone Absorption Spectroscopy under Environmental Fluctuations.

J Phys Chem B 2021 Jun 4. Epub 2021 Jun 4.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, China.

Ultraviolet (UV) absorption spectra are commonly used for characterizing the global structure of proteins. However, the theoretical interpretation of UV spectra is hindered by the large number of required expensive ab initio calculations of excited states spanning a huge conformation space. We present a machine-learning (ML) protocol for far-UV (FUV) spectra of proteins, which can predict FUV spectra of proteins with comparable accuracy to density functional theory (DFT) calculations but with 3-4 orders of magnitude reduced computational cost. Read More

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Through bonds or contacts? Mapping protein vibrational energy transfer using non-canonical amino acids.

Nat Commun 2021 06 2;12(1):3284. Epub 2021 Jun 2.

Institute of Biophysics, Goethe University Frankfurt, Frankfurt/Main, Germany.

Vibrational energy transfer (VET) is essential for protein function. It is responsible for efficient energy dissipation in reaction sites, and has been linked to pathways of allosteric communication. While it is understood that VET occurs via backbone as well as via non-covalent contacts, little is known about the competition of these two transport channels, which determines the VET pathways. Read More

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PSD-95 protects synapses from β-amyloid.

Cell Rep 2021 Jun;35(9):109194

Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California, San Diego, San Diego, CA 92093, USA.

Beta-amyloid (Aβ) depresses excitatory synapses by a poorly understood mechanism requiring NMDA receptor (NMDAR) function. Here, we show that increased PSD-95, a major synaptic scaffolding molecule, blocks the effects of Aβ on synapses. The protective effect persists in tissue lacking the AMPA receptor subunit GluA1, which prevents the confounding synaptic potentiation by increased PSD-95. Read More

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Isolation, Physicochemical Properties, and Structural Characteristics of Arabinoxylan from Hull-Less Barley.

Molecules 2021 May 19;26(10). Epub 2021 May 19.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.

Arabinoxylan (HBAX-60) was fractioned from alkaline-extracted arabinoxylan (HBAX) in the whole grain of hull-less barley ( L. Hook. f. Read More

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Hybrid Cyclobutane/Proline-Containing Peptidomimetics: The Conformational Constraint Influences Their Cell-Penetration Ability.

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Departament de Química, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.

A new family of hybrid β,γ-peptidomimetics consisting of a repetitive unit formed by a chiral cyclobutane-containing -β-amino acid plus a -functionalized -γ-amino-l-proline joined in alternation were synthesized and evaluated as cell penetrating peptides (CPP). They lack toxicity on the human tumoral cell line HeLa, with an almost negligible cell uptake. The dodecapeptide showed a substantial microbicidal activity on parasites at 50 µM but with a modest intracellular accumulation. Read More

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X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.

Protein Sci 2021 May 30. Epub 2021 May 30.

Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

Evolutionary selection ensures specificity and efficiency in dynamic metastable macromolecular machines that repair DNA damage without releasing toxic and mutagenic intermediates. Here we examine non-homologous end joining (NHEJ) as the primary conserved DNA double-strand break (DSB) repair process in human cells. NHEJ has exemplary key roles in networks determining the development, outcome of cancer treatments by DSB-inducing agents, generation of antibody and T-cell receptor diversity, and innate immune response for RNA viruses. Read More

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Stereochemical Control Yields Mucin Mimetic Polymers.

ACS Cent Sci 2021 Apr 30;7(4):624-630. Epub 2021 Mar 30.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight -glycoproteins that adopt extended linear structures. Read More

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Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor.

Nucleic Acids Res 2021 May 29. Epub 2021 May 29.

Dept. of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Double-stranded DNA viruses package their genomes into pre-assembled capsids using virally-encoded ASCE ATPase ring motors. We present the first atomic-resolution crystal structure of a multimeric ring form of a viral dsDNA packaging motor, the ATPase of the asccφ28 phage, and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Based on these results, and previous single-molecule data and cryo-EM reconstruction of the homologous φ29 motor, we propose an overall packaging model that is driven by helical-to-planar transitions of the ring motor. Read More

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Coordination-induced spontaneous resolution of a TPPE-based MOF and its use as a crystalline sponge in guest determination.

Dalton Trans 2021 Jun;50(21):7186-7190

Department of Chemistry, Anhui Normal University, Wuhu 241000, P. R. China.

In this work, by virtue of a coordination-induced fixation of the propeller-like conformation of the tetraphenylethylene (TPE) backbone, we achieved a spontaneous resolution of conglomerate-forming enantiomers of [Co(TPPE)Cl2]·4DMF (1M and 1P), as unambiguously probed by single-crystal X-ray crystallography. Benefitting from the robust, accessible, and electron-rich 1D channels, the chiral MOF turned out to be a good 'crystalline sponge' to adsorb and determine six liquid guests, of which two (2-butanol and 2-butylamine) are crystallized in an enantiospecific manner. Read More

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Mechanism of recognition of parallel G-quadruplexes by DEAH/RHAU helicase DHX36 explored by molecular dynamics simulations.

Comput Struct Biotechnol J 2021 23;19:2526-2536. Epub 2021 Apr 23.

Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw, Poland.

Because of high stability and slow unfolding rates of G-quadruplexes (G4), cells have evolved specialized helicases that disrupt these non-canonical DNA and RNA structures in an ATP-dependent manner. One example is DHX36, a DEAH-box helicase, which participates in gene expression and replication by recognizing and unwinding parallel G4s. Here, we studied the molecular basis for the high affinity and specificity of DHX36 for parallel-type G4s using all-atom molecular dynamics simulations. Read More

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Structural coordinates: A novel approach to predict protein backbone conformation.

PLoS One 2021 20;16(5):e0239793. Epub 2021 May 20.

Engelhardt Institute of Molecular Biology, Moscow, Russia.

Motivation: Local protein structure is usually described via classifying each peptide to a unique class from a set of pre-defined structures. These classifications may differ in the number of structural classes, the length of peptides, or class attribution criteria. Most methods that predict the local structure of a protein from its sequence first rely on some classification and only then proceed to the 3D conformation assessment. Read More

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Autofluorescence of Amyloids Determined by Enantiomeric Composition of Peptides.

J Phys Chem B 2021 06 19;125(21):5502-5510. Epub 2021 May 19.

Advanced Materials Engineering and Modelling Group, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.

Amyloid fibrils are peptide or protein aggregates possessing a cross-β-sheet structure. They possess intrinsic fluorescence property, which is still not fully understood. Herein, we compare structural and optical properties of fibrils formed from L- and D-enantiomers of the (105-115) fragment of transthyretin (TTR) and from their racemic mixture. Read More

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Nanomechanics of self-assembled DNA building blocks.

Nanoscale 2021 May;13(20):9371-9380

INM - Leibniz Institute for New Materials, Campus D22, 66123 Saarbrücken, Germany.

DNA has become a powerful platform to design functional nanodevices. DNA nanodevices are often composed of self-assembled DNA building blocks that differ significantly from the structure of native DNA. In this study, we present Flow Force Microscopy as a massively parallel approach to study the nanomechanics of DNA self-assemblies on the single-molecular level. Read More

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The structure, conformation, and hypoglycemic activity of a novel heteropolysaccharide from the blackberry fruit.

Food Funct 2021 May 17. Epub 2021 May 17.

School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China. and SCUT-Zhuhai Institute of Modern Industrial Innovation, Zhuhai 519715, China and Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Guangzhou 510640, China and Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), Guangzhou 510640, China.

A novel heteropolysaccharide fraction (BBP-24-3) with a relative molecular weight of 145.1 kDa was isolated from blackberry fruits. The BBP-24-3 was mainly composed of arabinose, glucose, and galacturonic acid with a ratio of 5. Read More

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Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.

Nat Commun 2021 05 14;12(1):2812. Epub 2021 May 14.

Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Read More

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Pairing a high-resolution statistical potential with a nucleobase-centric sampling algorithm for improving RNA model refinement.

Nat Commun 2021 05 13;12(1):2777. Epub 2021 May 13.

Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Drive, Southport, QLD, Australia.

Refining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years' efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined "native" structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base-base, base-oxygen and oxygen-oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. Read More

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Developments and Ongoing Challenges for Analysis of Surface-Bound Proteins.

Annu Rev Anal Chem (Palo Alto Calif) 2021 May 12. Epub 2021 May 12.

Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark; email:

Proteins at surfaces and interfaces play important roles in the function and performance of materials in applications ranging from diagnostic assays to biomedical devices. To improve the performance of these materials, detailed molecular structure (conformation and orientation) along with the identity and concentrations of the surface-bound proteins on those materials must be determined. This article describes radiolabeling, surface plasmon resonance, quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy, secondary ion mass spectrometry, sum frequency generation spectroscopy, and computational techniques along with the information each technique provides for characterizing protein films. Read More

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Tryptophan Operon Diversity Reveals Evolutionary Trends among Geographically Disparate Chlamydia trachomatis Ocular and Urogenital Strains Affecting Tryptophan Repressor and Synthase Function.

mBio 2021 May 11;12(3). Epub 2021 May 11.

Department of Pediatrics, University of California San Francisco, Oakland, California, USA

The obligate intracellular pathogen () is the leading cause of bacterial sexually transmitted infections and blindness globally. To date, urogenital strains are considered tryptophan prototrophs, utilizing indole for tryptophan synthesis within a closed-conformation tetramer comprised of two α (TrpA)- and two β (TrpB)-subunits. In contrast, ocular strains are auxotrophs due to mutations in TrpA, relying on host tryptophan pools for survival. Read More

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Isolation and structure characterization of a low methyl-esterified pectin from the tuber of Dioscorea opposita Thunb.

Food Chem 2021 Oct 20;359:129899. Epub 2021 Apr 20.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology Nanchang, Nanchang University, Nanchang, Jiangxi Province 330047, China. Electronic address:

A low methyl-esterified pectin (33.2% methyl-esterification degree) was isolated from the tuber of Dioscorea opposita Thunb., which was an edible and medicinal material in China. Read More

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October 2021

Potential of Raman spectroscopic techniques to study proteins.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 20;258:119712. Epub 2021 Apr 20.

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bengaluru 560 012, Karnataka, India; Department of Instrumentation & Applied Physics, Indian Institute of Science, Bengaluru 560 012, Karnataka, India. Electronic address:

Proteins are large, complex molecules responsible for various biological processes. However, protein misfolding may lead to various life-threatening diseases. Therefore, it is vital to understand the shape and structure of proteins. Read More

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September 2021

Redox-Mediated Reversible Supramolecular Assemblies Driven by Switch and Interplay of Peptide Secondary Structures.

Biomacromolecules 2021 Jun 7;22(6):2563-2572. Epub 2021 May 7.

CAS Center of Excellence for Nanoscience, Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

The construction of reversible supramolecular self-assembly remains a significant challenge. Here, we demonstrate the redox-triggered reversible supramolecular self-assembly governed by the "check and balance" of two secondary conformations within a brushlike peptide-selenopolypeptide conjugate. The conjugate constitutes a polypeptide backbone whose side chain contains selenoether functional moieties and double bonds to be readily grafted with β-sheet-prone short-peptide NapFFC. Read More

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Protein folding - seeing is deceiving.

George D Rose

Protein Sci 2021 May 2. Epub 2021 May 2.

T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.

This Perspective is intended to raise questions about the conventional interpretation of protein folding. According to the conventional interpretation, developed over many decades, a protein population can visit a vast number of conformations under unfolding conditions, but a single dominant native population emerges under folding conditions. Accordingly, folding comes with a substantial loss of conformational entropy. Read More

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MRCKβ links Dasm1 to actin rearrangements to promote dendrite development.

J Biol Chem 2021 Apr 29:100730. Epub 2021 Apr 29.

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

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. Read More

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Conformational and Immunogenicity Studies of the Serogroup 6 O-Antigen: The Effect of O-Acetylation.

Vaccines (Basel) 2021 Apr 27;9(5). Epub 2021 Apr 27.

Department of Computer Science, University of Cape Town, Rondebosch 7701, South Africa.

The pathogenic bacterium is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against . Read More

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