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Protein chemistry

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https://www.readbyqxmd.com/read/29328784/dna-encoded-chemical-libraries-a-selection-system-based-on-endowing-organic-compounds-with-amplifiable-information
#1
Dario Neri, Richard A Lerner
The discovery of organic ligands that bind specifically to proteins is a central problem in chemistry, biology, and the biomedical sciences. The encoding of individual organic molecules with distinctive DNA tags, serving as amplifiable identification bar codes, allows the construction and screening of combinatorial libraries of unprecedented size, thus facilitating the discovery of ligands to many different protein targets. Fundamentally, one links powers of genetics and chemical synthesis. After the initial description of DNA-encoded chemical libraries in 1992, several experimental embodiments of the technology have been reduced to practice...
January 12, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29328673/fluorescent-proteins-detect-host-structural-rearrangements-via-electrostatic-mechanism
#2
Lena Simine, Heiko Lammert, Li Sun, Jose Nelson Onuchic, Peter J Rossky
The rational design of genetically encoded fluorescent bio-sensors, which can detect rearrangements of target proteins via interdomain allostery, is hindered by the absence of mechanistic understanding of the underlying photo-physics. Here, we focus on the modulation of fluorescence by mechanical perturbation in a popular biological probe: enhanced Green Fluorescent Protein (eGFP). Using a combination of molecular dynamics (MD) simulations and quantum chemistry, and a set of physically motivated assumptions, we construct a map of fluorescence quantum yield as a function of a 2D electric field imposed by the protein environment on the fluorophore...
January 12, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29328627/effect-of-surface-chemistry-and-associated-protein-corona-on-the-long-term-biodegradation-of-iron-oxide-nanoparticles-in-vivo
#3
Grazyna Stepien, María Moros, Marta Perez-Hernandez, Marta Monge, Lucía Gutiérrez, Raluca Maria M Fratila, Marcelo Las Heras, Sebastian Menao Guillen, Juan Jose Puente Lanzarote, Conxita Solans, Julián Pardo, Jesús M De La Fuente
Protein corona formed on the surface of nanoparticle in biological medium determines its behavior in vivo. Here, iron oxide nanoparticles containing the same core and shell, but bearing two different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months, were investigated. Although both types of nanoparticles bound a similar amount of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo...
January 12, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29326245/fatty-acyl-recognition-and-transfer-by-an-integral-membrane-s-acyltransferase
#4
Mitra S Rana, Pramod Kumar, Chul-Jin Lee, Raffaello Verardi, Kanagalaghatta R Rajashankar, Anirban Banerjee
DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29325626/fragile-x-syndrome-and-fragile-x-associated-tremor-ataxia-syndrome
#5
Deborah A Hall, Elizabeth Berry-Kravis
Fragile X-associated disorders encompass several conditions, which are caused by expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or >200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures. Fragile X-associated tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29323892/same-substrate-many-reactions-oxygen-activation-in-flavoenzymes
#6
Elvira Romero, J Rubén Gómez Castellanos, Giovanni Gadda, Marco W Fraaije, Andrea Mattevi
Over time, organisms have evolved strategies to cope with the abundance of dioxygen on Earth. Oxygen-utilizing enzymes tightly control the reactions involving O2 mostly by modulating the reactivity of their cofactors. Flavins are extremely versatile cofactors that are capable of undergoing redox reactions by accepting either one electron or two electrons, alternating between the oxidized and the reduced states. The physical and chemical principles of flavin-based chemistry have been investigated widely. In the following pages we summarize the state of the art on a key area of research in flavin enzymology: the molecular basis for the activation of O2 by flavin-dependent oxidases and monooxygenases...
January 11, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#7
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29323490/activity-related-microsecond-dynamics-revealed-by-temperature-jump-f%C3%A3-rster-resonance-energy-transfer-measurements-on-thermophilic-alcohol-dehydrogenase
#8
Morgan B Vaughn, Jianyu Zhang, Thomas G Spiro, R Brian Dyer, Judith P Klinman
Previous studies of a thermophilic alcohol dehydrogenase (ht-ADH) demonstrated a range of discontinuous transitions at 30 °C that include catalysis, kinetic isotope effects, protein hydrogen-deuterium exchange rates, and intrinsic fluorescence properties. Using the Förster resonance energy transfer response from a Trp-NADH donor-acceptor pair in T-jump studies of ht-ADH, we now report microsecond protein motions that can be directly related to active site chemistry. Two distinctive transients are observed: a slow, kinetic process lacking a temperature break, together with a faster transient that is only detectable above 30 °C...
January 11, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29321951/utility-of-the-phenacyl-protecting-group-in-traceless-protein-semisynthesis-through-ligation-desulfurization-chemistry
#9
Maria Matveenko, Stefanie Hackl, Christian F W Becker
Semisynthesis of proteins via expressed protein ligation is a widely applicable method, even more so because of the possibility of ligation at non-cysteine sites using β-mercapto amino acids that can be converted to the corresponding native amino acids by desulfurization. A drawback of this ligation- desulfurization approach is the removal of any unprotected native cysteine residues within the ligated protein segments. Here, we show that the phenacyl (PAc) moiety can be successfully used to protect cysteines within recombinantly generated protein segments...
January 2018: ChemistryOpen
https://www.readbyqxmd.com/read/29320869/challenges-and-opportunities-for-small-molecule-fluorescent-probes-in-redox-biology-applications
#10
Xiqian Jiang, Lingfei Wang, Shaina Laufer Carroll, Jianwei Chen, Meng C Wang, Jin Wang
SIGNIFICANCE: The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development allowing more selective and quantitative detection of ROS/RNS, especially in live cells...
January 10, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29320632/increasing-the-stability-of-recombinant-human-green-cone-pigment
#11
Timothy S Owen, David Salom, Wenyu Sun, Krzysztof Palczewski
Three types of cone cells exist in the human retina, each containing a different pigment responsible for the initial step of photo-transduction. These pigments are distinguished by their specific absorbance maxima, 425 nm (blue), 530 nm (green) and 560 nm (red). Each pigment contains a common chromophore, 11-cis-retinal covalently bound to an opsin protein via a Schiff base. The 11-cis-retinal protonated Schiff base has an absorbance maxima at 440 nm in methanol. Unfortunately, the chemistry allowing the same chromophore interacting with different opsin proteins to tune the absorbance of the resulting pigments to distinct λmax values is poorly understood...
January 10, 2018: Biochemistry
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#12
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29319889/epitope-targeted-macrocyclic-peptide-ligand-with-picomolar-cooperative-binding-to-interleukin-17f
#13
Bert T Lai, Jeré A Wilson, Jacquie Malette Loredo, Suresh M Pitram, Nicole A LaBerge, James R Heath, Heather Agnew
The IL-17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. We developed epitope-targeted ligands designed for differential detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and unique epitopes on IL-17F and IL-17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5-mer variable regions...
January 10, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29319318/dominant-albumin-surface-interactions-under-independent-control-of-surface-charge-and-wettability
#14
Shanshan Guo, Dicky Pranantyo, En-Tang Kang, Xian Jun Loh, Xiaoying Zhu, Dominik Jańczewski, Koon-Gee Neoh
Understanding protein adsorption behaviors on solid surfaces constitutes an important step towards development of efficacious and biocompatible medical devices. Both surface charge and wettability have been shown to influence protein adsorption attributes including the kinetics, quantities, deformation and reversibility. However, determining the dominant interaction in these surface-induced phenomena is challenging due to the complexity of inter-related mechanisms at the liquid/solid interface. Herein, we reveal the dominant interfacial forces in these essential protein adsorption attributes under the influence of a combination of surface charge and wettability using a quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM)-based force spectroscopy on a series of model surfaces...
January 10, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29317496/a-functional-link-between-nad-homeostasis-and-n-terminal-protein-acetylation-in-saccharomyces-cerevisiae
#15
Trevor Croft, Christol James Theoga Raj, Michelle Salemi, Brett S Phinney, Su-Ju Lin
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite participating in cellular redox chemistry and signaling, and the complex regulation of NAD+ metabolism is not yet fully understood. To investigate this, we established a NAD+-intermediate specific reporter system to identify factors required for salvage of metabolically-linked nicotinamide (NAM) and nicotinic acid (NA). Mutants lacking components of the NatB complex, NAT3 and MDM20, appeared as hits in this screen. NatB is an Nα-terminal-acetyltransferase responsible for acetylation of the amino terminus of specific Met-retained peptides...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29317070/hypothesis-for-the-cause-and-therapy-of-neurodegenerative-diseases
#16
Philip Serwer
The cause and therapy of neurodegenerative diseases remain unsolved puzzles. These diseases are correlated with presence of beta sheet-rich amyloid assemblies. Here, I derive and assemble puzzle pieces to obtain a loose end-tying hypothesis for cause with direct implications for therapy. I use the following extrapolations to find connectable puzzle pieces: (a) the traditional extrapolation that amyloid/amyloid precursors cause disease, (b) a recent extrapolation that amyloid-forming proteins, some of which are virus protein homologs, are components of an empirically obscure innate immune system that counters insults, including those by both viruses and bacteria, (c) a new extrapolation that various insults produce assemblies with structural features in common and that amyloid-forming, innate immune system proteins recognize these features and, then, counter insults by co-assembly, (d, 1) a second new extrapolation that beta sheet is a common structural feature and is extended during insult-neutralizing co-assembly and (d, 2) an appendix, derived from studies of phages T3 and T4, that most insult-produced assemblies are obscure to current biochemical analysis...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316387/solid-phase-synthesis-of-%C3%AE-amino-ketones-via-dna-compatible-organocatalytic-mannich-reactions
#17
Nam Tran Hoang, Thomas Kodadek
One-bead-one-compound (OBOC) libraries constructed by solid-phase split-and-pool synthesis are a valuable source of protein ligands. Most OBOC libraries are comprised of oligoamides, particularly peptides, peptoids and peptoid-inspired molecules. Further diversification of the chemical space covered by OBOC libraries is desirable. Towards this end, we report here the efficient proline-catalyzed asymmetric Mannich reaction between immobilized aldehydes and soluble ketones and anilines. The reaction conditions do not compromise the amplification of DNA by the PCR...
January 9, 2018: ACS Combinatorial Science
https://www.readbyqxmd.com/read/29315702/strategies-to-target-the-hedgehog-signaling-pathway-for-cancer-therapy
#18
REVIEW
Minhang Xin, Xinyue Ji, Ladie Kimberly De La Cruz, Suresh Thareja, Binghe Wang
Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29314832/oligonucleotide-peptide-complexes-phase-control-by-hybridization
#19
Jeffrey R Vieregg, Michael Lueckheide, Amanda Brittany Marciel, Lorraine Leon, Alex J Bologna, Josean Reyes Rivera, Matthew V Tirrell
When oppositely-charged polymers are mixed, counterion release drives phase separation; understanding this process is a key unsolved problem in polymer science and biophysical chemistry, particularly for nucleic acids, polyanions whose biological functions are intimately related to their high charge density. In the cell, complexation by basic proteins condenses DNA into chromatin, and membraneless organelles formed by liquid-liquid phase separation of RNA and proteins perform vital functions and have been linked to disease...
January 9, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29314649/approaching-the-thermodynamic-view-of-protein-folding-through-the-reproduction-of-anfinsen-s-experiment-by-undergraduate-physical-biochemistry-students
#20
Andres Fernandez-Reche, Eva S Cobos, Irene Luque, Javier Ruiz-Sanz, Jose C Martinez
In 1972 Christian B. Anfinsen received the Nobel Prize in Chemistry for "…his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation." The understanding of this principle is crucial for physical biochemistry students, since protein folding studies, bio-computing sciences and protein design approaches are founded on such a well-demonstrated connection. Herein, we describe a detailed and easy-to-follow experiment to reproduce the most relevant assays carried out at Anfinsen's laboratory in the 60s...
January 4, 2018: Biochemistry and Molecular Biology Education
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