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Trends in Biochemical Sciences

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https://www.readbyqxmd.com/read/29970330/from-the-wave-equation-to-biomolecular-structure-and-dynamics
#1
Suren A Tatulian
The multiscale models for complex chemical systems constitute a powerful computational tool to describe biomolecular structure and dynamics, including enzymatic reactions. Here, the development of this method is presented as a miraculous chain of events, involving astoundingly lucky encounters of brilliant minds such as Planck, Schrödinger, Pauling, Karplus, Levitt, and Warshel.
June 30, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29941230/gene-regulatory-network-perturbation-by-genetic-and-epigenetic-variation
#2
REVIEW
Yongsheng Li, Daniel J McGrail, Juan Xu, Gordon B Mills, Nidhi Sahni, Song Yi
Gene regulatory networks underlie biological function and cellular physiology. Alternative splicing (AS) is a fundamental step in gene regulatory networks and plays a key role in development and disease. In addition to the identification of aberrant AS events, an increasing number of studies are focusing on molecular determinants of AS, including genetic and epigenetic regulators. We review here recent efforts to identify various deregulated AS events as well as their molecular determinants that alter biological functions, and discuss clinical features of AS and their druggable potential...
June 22, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29934030/reversible-spatial-and-temporal-control-over-protein-activity-using-light
#3
REVIEW
Mark W H Hoorens, Wiktor Szymanski
In biomedical sciences, the function of a protein of interest is investigated by altering its net activity and assessing the consequences for the cell or organism. To change the activity of a protein, a wide variety of chemical and genetic tools have been developed. The drawback of most of these tools is that they do not allow for reversible, spatial and temporal control. Here, we describe selected developments in photopharmacology that aim at establishing such control over protein activity through bioactive molecules with photo-controlled potency...
June 19, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29910019/epigenetic-editing-repurposing-for-rescue
#4
Hari R Singh
The epigenome editing framework provides an engineering approach to explore chromatin-based gene expression mechanisms. However, therapeutic utility of epigenetic editing-based systems has been lacking. A report in Cell (Liu et. al., 2018) shows that epigenetic editors can revert abnormal heterochromatin formation at the gene promoter leading to restoration of FMR1 gene expression, functionally rescuing fragile X syndrome (FXS), an otherwise unamenable genetic disorder.
June 14, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29895507/unraveling-endocrine-fgf-signaling-complex-to-combat-metabolic-diseases
#5
Yongde Luo, Weiqin Lu, Xiaokun Li
Metabolic homeostasis is critical to cellular and organismal health. The newly revealed crystal structures of the endocrine factors FGF21 and FGF23, in association with the glycosidase coreceptor Klotho and transmembrane tyrosine kinase FGFR, set a platform for structure-based novel drug design against common metabolic disorders.
June 9, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29807701/the-krebs-uric-acid-cycle-a-forgotten-krebs-cycle
#6
LETTER
Jack G Salway
Hans Kornberg wrote a paper entitled 'Krebs and his trinity of cycles' commenting that every school biology student knows of the Krebs cycle, but few know that Krebs discovered two other cycles. These are (i) the ornithine cycle (urea cycle), (ii) the citric acid cycle (tricarboxylic acid or TCA cycle), and (iii) the glyoxylate cycle that was described by Krebs and Kornberg. Ironically, Kornberg, codiscoverer of the 'glyoxylate cycle', overlooked a fourth Krebs cycle - (iv) the uric acid cycle.
May 25, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29803538/modeling-the-embrace-of-a-mutator-apobec-selection-of-nucleic-acid-ligands
#7
REVIEW
Jason D Salter, Harold C Smith
The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site...
May 23, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29789219/cap-independent-translation-what-s-in-a-name
#8
REVIEW
Ivan N Shatsky, Ilya M Terenin, Victoria V Smirnova, Dmitri E Andreev
Eukaryotic translation initiation relies on the m7 G cap present at the 5' end of all mRNAs. Some viral mRNAs employ alternative mechanisms of initiation based on internal ribosome entry. The 'IRES ideology' was adopted by researchers to explain the differential translation of cellular mRNAs when the cap recognition is suppressed. However, some cellular IRESs have already been challenged and others are awaiting their validation. As an alternative cap-independent mechanism, we propose adopting the concept of cap-independent translation enhancers (CITEs) for mammalian mRNAs...
May 19, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29735398/fatty-acid-oxidation-in-cell-fate-determination
#9
Jianhua Xiong
Mitochondrial fatty acid β-oxidation (FAO) is a major catabolic process that degrades long-chain fatty acids. Recent reports reveal a broad role for FAO in cell fate control in endothelial cells, immune cells, and cancer cells. Concurrently, unique molecular pathways influenced by FAO have been identified that alter cell fate decisions.
May 4, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29729937/highlighting-ir-spectrochemical-imaging-of-the-retina
#10
Ebrahim Aboualizadeh, Carol J Hirschmugl
An emerging application of mid-IR spectrochemical imaging of the retina is its utility in studying the highly localized biomolecular alterations in the chemistry of retinal cell layers associated with several pathological conditions. Spatially resolved IR images highlight simultaneous chemical composition of the entire span of the retina in a label-free manner.
May 2, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29709390/amazing-diversity-in-biochemical-roles-of-fe-ii-2-oxoglutarate-oxygenases
#11
REVIEW
Caitlyn Q Herr, Robert P Hausinger
Since their discovery in the 1960s, the family of Fe(II)/2-oxoglutarate-dependent oxygenases has undergone a tremendous expansion to include enzymes catalyzing a vast diversity of biologically important reactions. Recent examples highlight roles in controlling chromatin modification, transcription, mRNA demethylation, and mRNA splicing. Others generate modifications in tRNA, translation factors, ribosomes, and other proteins. Thus, oxygenases affect all components of molecular biology's central dogma, in which information flows from DNA to RNA to proteins...
April 27, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29793809/dna-based-dynamic-reaction-networks
#12
REVIEW
Ting Fu, Yifan Lyu, Hui Liu, Ruizi Peng, Xiaobing Zhang, Mao Ye, Weihong Tan
Deriving from logical and mechanical interactions between DNA strands and complexes, DNA-based artificial reaction networks (RNs) are attractive for their high programmability, as well as cascading and fan-out ability, which are similar to the basic principles of electronic logic gates. Arising from the dream of creating novel computing mechanisms, researchers have placed high hopes on the development of DNA-based dynamic RNs and have strived to establish the basic theories and operative strategies of these networks...
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29789218/does-too-much-magic-lead-to-mitophagy
#13
Mohamed A Eldeeb, Richard P Fahlman
Neurodegeneration-associated hallmarks include an abundance of protein aggregates and amelioration of mitochondrial function. Despite the knowledge of molecular counteracting mechanisms, the molecular dialogue between protein aggregate accumulation and aberrant mitochondrial import is poorly understood. Recent work unraveled a novel role for the mitochondrial import machinery in regulating cytosolic proteostasis.
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29748115/kras-activating-signaling-triggers-arteriovenous-malformations
#14
LETTER
Feixiong Cheng, Ruth Nussinov
The underlying genetic causes and altered signaling pathways of brain arteriovenous malformations remain unknown. A study published in The New England Journal of Medicine reported that KRAS somatic mutations (p.Gly12Val/Asp) were identified in brain arteriovenous malformations of human subjects and endothelial cell-enriched cultures, which might specifically activate the MAPK (mitogen-activated protein kinase)-ERK (extracellular signal-regulated kinase) signaling pathway in brain endothelial cells.
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29735400/concept-of-dna-lesion-longevity-and-chromosomal-translocations
#15
REVIEW
Nicholas R Pannunzio, Michael R Lieber
A subset of chromosomal translocations related to B cell malignancy in human patients arises due to DNA breaks occurring within defined 20-600 base pair (bp) zones. Several factors influence the breakage rate at these sites including transcription, DNA sequence, and topological tension. These factors favor non-B DNA structures that permit formation of transient single-stranded DNA (ssDNA), making the DNA more vulnerable to agents such as the enzyme activation-induced cytidine deaminase (AID) and reactive oxygen species (ROS)...
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29735399/emerging-paradigm-of-intracellular-targeting-of-g-protein-coupled-receptors
#16
REVIEW
Madhu Chaturvedi, Justin Schilling, Alexandre Beautrait, Michel Bouvier, Jeffrey L Benovic, Arun K Shukla
G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures...
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29731341/architecture-of-prc2-holo-complexes
#17
Kendra R Vann, Tatiana G Kutateladze
Polycomb repressive complex 2 (PRC2) is a chief epigenetic regulator. In a new article, Chen et al. describe the crystal structure of the heterotetrameric PRC2 holo complex, which provides important mechanistic insights into the organization of its subunits and the association of PRC2 with chromatin.
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29716768/why-do-disordered-and-structured-proteins-behave-differently-in-phase-separation
#18
REVIEW
Huan-Xiang Zhou, Valery Nguemaha, Konstantinos Mazarakos, Sanbo Qin
Intracellular membraneless organelles and their myriad cellular functions have garnered tremendous recent interest. It is becoming well accepted that they form via liquid-liquid phase separation (LLPS) of protein mixtures (often including RNA), where the organelles correspond to a protein-rich droplet phase coexisting with a protein-poor bulk phase. The major protein components contain disordered regions and often also RNA-binding domains, and the disordered fragments on their own easily undergo LLPS. By contrast, LLPS for structured proteins has been observed infrequently...
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29685368/principles-of-chromosome-architecture-revealed-by-hi-c
#19
REVIEW
Kyle P Eagen
Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops...
June 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29673772/widespread-enhancer-activity-from-core-promoters
#20
REVIEW
Alejandra Medina-Rivera, David Santiago-Algarra, Denis Puthier, Salvatore Spicuglia
Gene expression in higher eukaryotes is precisely regulated in time and space through the interplay between promoters and gene-distal regulatory regions, known as enhancers. The original definition of enhancers implies the ability to activate gene expression remotely, while promoters entail the capability to locally induce gene expression. Despite the conventional distinction between them, promoters and enhancers share many genomic and epigenomic features. One intriguing finding in the gene regulation field comes from the observation that many core promoter regions display enhancer activity...
June 2018: Trends in Biochemical Sciences
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