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Current Opinion in Chemical Biology

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https://www.readbyqxmd.com/read/29331721/understanding-protein-drug-interactions-using-ion-mobility-mass-spectrometry
#1
REVIEW
Claire E Eyers, Matthias Vonderach, Samantha Ferries, Kiani Jeacock, Patrick A Eyers
Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecules, including clinically-relevant drugs, play in these processes...
January 10, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29306820/activity-based-sensing-fluorescent-probes-for-iron-in-biological-systems
#2
REVIEW
Allegra T Aron, Audrey G Reeves, Christopher J Chang
Iron is an essential nutrient for life, and its capacity to cycle between different oxidation states is required for processes spanning oxygen transport and respiration to nucleotide synthesis and epigenetic regulation. However, this same redox ability also makes iron, if not regulated properly, a potentially dangerous toxin that can trigger oxidative stress and damage. New methods that enable monitoring of iron in living biological systems, particularly in labile Fe2+ forms, can help identify its contributions to physiology, aging, and disease...
January 4, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29306688/ion-mobility-in-the-pharmaceutical-industry-an-established-biophysical-technique-or-still-niche
#3
REVIEW
Iain Dg Campuzano, Jennifer L Lippens
Over the past decade ion mobility (IM) coupled with mass spectrometry (MS) has emerged as a wide spread analytical technique, utilized in research areas ranging from small molecule to proteins analyzed under native-MS and solution conditions. The ion-neutral collision cross section (Ω) derived from an IM experiment can be used to make inferences about the ion's size, shape and charge distribution, when compared to molecular dynamic (MD) or quantum mechanically (QM) derived candidate structures. IM can also be used as an orthogonal separation technique when coupled with liquid chromatographic (LC) separations...
January 4, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29288996/mass-spectrometry-beyond-the-native-state
#4
REVIEW
Shane A Chandler, Justin Lp Benesch
Native mass spectrometry allows the study of proteins by probing in vacuum the interactions they form in solution. It is a uniquely useful approach for structural biology and biophysics due to the high resolution of separation it affords, allowing the concomitant interrogation of multiple protein components with high mass accuracy. At its most basic, native mass spectrometry reports the mass of intact proteins and the assemblies they form in solution. However, the opportunities for more detailed characterisation are extensive, enabled by the exquisite control of ion motion that is possible in vacuum...
December 27, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29287234/improving-the-discovery-of-secondary-metabolite-natural-products-using-ion-mobility-mass-spectrometry
#5
REVIEW
Alexandra C Schrimpe-Rutledge, Stacy D Sherrod, John A McLean
Secondary metabolite discovery requires an unbiased, comprehensive workflow to detect unknown unknowns for which little to no molecular knowledge exists. Untargeted mass spectrometry-based metabolomics is a powerful platform, particularly when coupled with ion mobility for high-throughput gas-phase separations to increase peak capacity and obtain gas-phase structural information. Ion mobility data are described by the amount of time an ion spends in the drift cell, which is directly related to an ion's collision cross section (CCS)...
December 26, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29278779/transaminases-for-chiral-amine-synthesis
#6
REVIEW
Andrew Gomm, Elaine O'Reilly
Amine transaminases are important biocatalysts for the synthesis of chiral primary amines. Unlike many enzymes that have been employed for the synthesis of optically active amines, amine transaminases are capable of asymmetric synthesis and do not rely on costly cofactors that must be regenerated in situ. However, their application as general catalysts for the preparation of amines is hampered by a limited substrate scope, substrate and (co)product inhibition and difficulties associated with displacing challenging reaction equilibrium...
December 23, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29275291/biocatalytic-reduction-of-activated-cc-bonds-and-beyond-emerging-trends
#7
REVIEW
Christoph K Winkler, Kurt Faber, Mélanie Hall
The biocatalytic reduction of activated CC-bonds is dominated by ene-reductases from the Old Yellow Enzyme family, which gained broad practical use owing to exquisite stereoselectivity combined with wide substrate scope. Protein diversity is fostered by mining distinct protein classes and by implementing protein engineering techniques. Recent efforts are focusing on expanding the chemical complexity of the product portfolio, either through substrate functionalization or design of multi-step reactions. This review also highlights unusual chemistries catalyzed by ene-reductases and presents emerging methodologies developed to bypass the need of natural nicotinamide cofactors...
December 21, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29275290/genetically-encoded-fluorescent-sensors-for-measuring-transition-and-heavy-metals-in-biological-systems
#8
REVIEW
Ziyang Hao, Rongfeng Zhu, Peng R Chen
Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM homeostasis in both physiological and pathological settings. Here we summarize the recent development of genetically encoded fluorescent sensors for intracellular detection of TMs such as zinc and copper, as well as heavy metals including lead, cadmium, mercury, and arsenic...
December 21, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29275246/advances-in-mass-spectrometry-imaging-coupled-to-ion-mobility-spectrometry-for-enhanced-imaging-of-biological-tissues
#9
REVIEW
Marta Sans, Clara L Feider, Livia S Eberlin
Tissues present complex biochemical and morphological composition associated with their various cell types and physiological functions. Mass spectrometry (MS) imaging technologies are powerful tools to investigate the molecular information from biological tissue samples and visualize their complex spatial distributions. Coupling of gas-phase ion mobility spectrometry (IMS) technologies to MS imaging has been increasingly explored to improve performance for biological tissue imaging. This approach allows improved detection of low abundance ions and separation of isobaric molecular species, thus resulting in more accurate determination of the spatial distribution of molecular ions...
December 21, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29258054/recent-advances-in-enzymatic-oxidation-of-alcohols
#10
REVIEW
Ji Liu, Shuke Wu, Zhi Li
Enzymatic alcohol oxidation plays an important role in chemical synthesis. In the past two years, new alcohol oxidation enzymes were developed through genome-mining and protein engineering, such as new copper radical oxidases with broad substrate scope, alcohol dehydrogenases with altered cofactor preference and a flavin-dependent alcohol oxidase with enhanced oxygen coupling. New cofactor recycling methods were reported for alcohol dehydrogenase-catalyzed oxidation with photocatalyst and coupled glutaredoxin-glutathione reductase as promising examples...
December 16, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29248736/contemporary-glycomic-approaches-using-ion-mobility-mass-spectrometry
#11
REVIEW
Kelsey A Morrison, Brian H Clowers
Characterization of complex oligosaccharides has historically required extensive sample handling and separations before analysis using nuclear magnetic resonance spectroscopy and electron impact mass spectra following hydrolysis, derivatization, and gas chromatographic separation. Advances in liquid chromatography separations and tandem mass spectrometry have expanded the range of intact glycan analysis, but carbohydrate structure and conformation-integral chemical characteristics-are often difficult to assess with minimal amounts of sample in a rapid fashion...
December 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29245143/functionalization-of-protein-crystals-with-metal-ions-complexes-and-nanoparticles
#12
REVIEW
Satoshi Abe, Basudev Maity, Takafumi Ueno
Self-assembled proteins have specific functions in biology. With inspiration provided by natural protein systems, several artificial protein assemblies have been constructed via site-specific mutations or metal coordination, which have important applications in catalysis, material and bio-supramolecular chemistry. Similar to natural protein assemblies, protein crystals have been recognized as protein assemblies formed of densely-packed monomeric proteins. Protein crystals can be functionalized with metal ions, metal complexes or nanoparticles via soaking, co-crystallization, creating new metal binding sites by site-specific mutations...
December 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29241076/magnifying-ion-mobility-spectrometry-mass-spectrometry-measurements-for-biomolecular-structure-studies
#13
REVIEW
Sandra N Majuta, Hossein Maleki, Ahmad Kiani Karanji, Kushani Attanyake, Elinore Loch, Stephen J Valentine
Ion mobility spectrometry-mass spectrometry (IMS-MS) provides information about the structures of gas-phase ions in the form of a collision cross section (CCS) with a neutral buffer gas. Indicating relative ion size, a CCS value alone is of limited utility. Although such information can be used to propose different conformer types, finer details of structure are not captured. The increased accessibility of IMS-MS measurements with commercial instrumentation in recent years has ballooned its usage in combination with separate measurements to provide enhanced data from which greater structural inferences can be drawn...
December 11, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29223060/recent-advances-in-lipid-separations-and-structural-elucidation-using-mass-spectrometry-combined-with-ion-mobility-spectrometry-ion-molecule-reactions-and-fragmentation-approaches
#14
REVIEW
Xueyun Zheng, Richard D Smith, Erin S Baker
Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed knowledge about distinct lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple acyl chain connectivities (sn-1, sn-2, or sn-3), double bond positions and orientations (cis or trans), and functional group stereochemistries (R versus S)...
December 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29223008/single-molecule-force-spectroscopy-a-new-tool-for-bioinorganic-chemistry
#15
REVIEW
Hongbin Li, Peng Zheng
Metalloproteins are essential in biology. The incorporation of metal ion into metalloproteins significantly expands protein functionality and enhances protein stability. Over the last few years, atomic force microscopy-based single molecule force spectroscopy (SMFS) has evolved into a unique tool allowing for probing metalloproteins and metalligand bonds one molecule/bond at a time. Mechanical strength of a wide variety of metalligand bonds has been measured in metal-ligand complexes as well as in metalloproteins, providing detailed information of their underlying free energy profiles and the influence of the protein environment on the bond strength...
December 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29207278/collision-induced-unfolding-of-isolated-proteins-in-the-gas-phase-past-present-and-future
#16
REVIEW
Sugyan M Dixit, Daniel A Polasky, Brandon T Ruotolo
Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences...
December 2, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29202341/bridging-the-structural-gap-of-glycoproteomics-with-ion-mobility-spectrometry
#17
REVIEW
Abhigya Mookherjee, Miklos Guttman
Over the past two decades mass spectrometry (MS) has enabled high throughput studies on the level of a complex proteome. While it has similarly advanced glycobiology, the level of progress has been more restrained. This is in large part due to the diversity and complexity of carbohydrate structures. While MS is now routinely used for glycobiology, it suffers from a critical limitation, that is the inability to resolve isobaric structures. Since so many structurally and functionally distinct carbohydrates are indistinguishable by MS, additional techniques are needed for detailed structural analysis...
December 1, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29197255/methane-to-bioproducts-the-future-of-the-bioeconomy
#18
REVIEW
Allison J Pieja, Molly C Morse, Andrew J Cal
Methanotrophs have been studied since the 1970s, but interest has increased tremendously in recent years due to their potential to transform methane into valuable bioproducts. The vast quantity of available methane and the low price of methane as natural gas have helped to spur this interest. The most well-studied, biologically-derived products from methane include methanol, polyhydroxyalkanoates, and single cell protein. However, many other high-interest chemicals such as biofuels or high-value products such as ectoine could be made industrially relevant through metabolic engineering...
November 29, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29175532/mitochondrial-dynamics-tracking-with-iridium-iii-complexes
#19
REVIEW
Yu Chen, Thomas W Rees, Liangnian Ji, Hui Chao
Since the discovery of mitochondrial dynamics, demand for dyes able to track this process has been a great. In contrast to static imaging, dynamic tracking requires superior photostability, low cytotoxicity and high resistance to the loss of mitochondrial membrane potential as well as appreciable tolerance to environmental changes. Recently, a variety of phosphorescent Ir(III) complexes have been found to localize in mitochondria and their applications as mitochondrial dynamics trackers have been assessed in cell monolayers, 3D MCSs and live animals...
November 22, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29169048/protein-lipoylation-an-evolutionarily-conserved-metabolic-regulator-of-health-and-disease
#20
REVIEW
Elizabeth A Rowland, Caroline K Snowden, Ileana M Cristea
Lipoylation is a rare, but highly conserved lysine posttranslational modification. To date, it is known to occur on only four multimeric metabolic enzymes in mammals, yet these proteins are staples in the core metabolic landscape. The dysregulation of these mitochondrial proteins is linked to a range of human metabolic disorders. Perhaps most striking is that lipoylation itself, the proteins that add or remove the modification, as well as the proteins it decorates are all evolutionarily conserved from bacteria to humans, highlighting the importance of this essential cofactor...
November 20, 2017: Current Opinion in Chemical Biology
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