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Current Opinion in Chemical Biology

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https://www.readbyqxmd.com/read/28923586/genetic-code-asymmetry-supports-diversity-through-experimentation-with-posttranslational-modifications
#1
REVIEW
James W Dennis
Protein N-glycosylation has been identified in all three domains of life presumably conserved for its early role in glycoprotein folding. However, the N-glycans added to proteins in the secretory pathway of multicellular organisms are remodeling in the Golgi, increasing structural diversity exponentially and adding new layers of functionality in immunity, metabolism and other systems. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families...
September 15, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28923279/needs-and-opportunities-in-bio-design-automation-four-areas-for-focus
#2
REVIEW
Evan Appleton, Douglas Densmore, Curtis Madsen, Nicholas Roehner
Bio-design automation (BDA) is an emerging field focused on computer-aided design, engineering principles, and automated manufacturing of biological systems. Here we discuss some outstanding challenges for bio-design that can be addressed by developing new tools for combinatorial engineering, equipment interfacing, next-generation sequencing, and workflow integration. These four areas, while not an exhaustive list of those that need to be addressed, could yield advances in bio-design, laboratory automation, and biometrology...
September 15, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28910721/an-amino-acid-domino-effect-orchestrates-clpp-s-conformational-states
#3
REVIEW
Matthias Stahl, Stephan A Sieber
Maintaining the cellular protein homeostasis means managing life on the brink of death. This balance is largely based on precise fine-tuning of enzyme activities. For instance, the ClpP protease possesses several conformational switches which are fundamental to regulating its activity. Efforts have focused on revealing the structural basis of ClpP's conformational control. In the last decade, several amino acid clusters have been identified and functionally linked to specific activation states. Researchers have now begun to couple these hotspots to one another, uncovering a global network of residues that switch in response to internal and external stimuli...
September 11, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28888143/synthetic-zwitterionic-polysaccharides
#4
REVIEW
Qingju Zhang, Herman S Overkleeft, Gijsbert A van der Marel, Jeroen Dc Codée
Zwitterionic polysaccharides (ZPSs) are a unique class of polysaccharides that are capable of eliciting a T-cell response after being processed by antigen presenting cells and presented on MHC II molecules. In addition, they have also been shown to be potent stimulators of the innate arm of the immune system. To unravel the molecular details of their remarkable immunological activity, various synthetic approaches to assemble fragments towards these polysaccharides have been reported. This review describes these efforts, illustrating the immense challenges presented by these inspiring structures...
September 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28869851/repurposing-ribosomes-for-synthetic-biology
#5
REVIEW
Yi Liu, Do Soon Kim, Michael C Jewett
The translation system is the cell's factory for protein biosynthesis, stitching together hundreds to thousands of amino acids into proteins, which are required for the structure, function, and regulation of living systems. The extraordinary synthetic capability of this system, which includes the ribosome and its associated factors required for polymerization, has driven extensive efforts to harness it for societal use in areas as diverse as energy, materials, and medicine. A powerful example is recombinant protein production, which has impacted the lives of patients through the synthesis of biopharmaceuticals such as insulin...
August 31, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28802999/primordial-membranes-more-than-simple-container-boundaries
#6
REVIEW
Martin M Hanczyc, Pierre-Alain Monnard
Cellular membranes, which are self-assembled bilayer structures mainly composed of lipids, proteins and conjugated polysaccharides, are the defining feature of cell physiology. It is likely that the complexity of contemporary cells was preceded by simpler chemical systems or protocells during the various evolutionary stages that led from inanimate to living matter. It is also likely that primitive membranes played a similar role in protocell 'physiology'. The composition of such ancestral membranes has been proposed as mixtures of single hydrocarbon chain amphiphiles, which are simpler versions of modern lipids...
August 10, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28801102/editorial-overview-chemical-genetics-and-epigenetics
#7
EDITORIAL
Evripidis Gavathiotis, Ming-Ming Zhou
No abstract text is available yet for this article.
August 8, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28756083/editorial-overview-molecular-imaging-for-seeing-chemistry-in-biology
#8
EDITORIAL
Xing Chen, Yanyi Huang
No abstract text is available yet for this article.
July 26, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28735229/synthetic-antibody-mimics-for-the-inhibition-of-protein-ligand-interactions
#9
REVIEW
Christina Haußner, Johannes Lach, Jutta Eichler
The rational/structure-based design and/or combinatorial development of molecules capable of selectively binding to a protein, represents a promising strategy for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. The design of such protein binding molecules is often based on an antibody against the target protein, or involves the generation of smaller molecules that retain the binding characteristics of the antibody. Alternatively, protein binding molecules can be selected from protein libraries based on small, stably folded protein scaffolds presenting flexible loops, which are randomized in the libraries...
July 20, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28709120/advances-in-design-of-protein-folds-and-assemblies
#10
REVIEW
Ajasja Ljubetič, Helena Gradišar, Roman Jerala
Conceptual and computational advances triggered an explosion of designed protein structures in the recent years. Various protein fold geometries have been robustly designed with atomic accuracy, including protein folds unseen in nature. The same principles and tools have been extended to design multi-chain assemblies. By exploiting symmetry, mega-Dalton structures have been created with exciting potential applications for synthetic biology. In this review we focus on design of single chain and multi polypeptide chain assemblies of defined size and composition...
July 11, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28735187/progress-in-targeting-the-bcl-2-family-of-proteins
#11
REVIEW
Thomas P Garner, Andrea Lopez, Denis E Reyna, Adam Z Spitz, Evripidis Gavathiotis
The network of protein-protein interactions among the BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Anti-apoptotic BCL-2 proteins are considered promising targets for drug discovery and exciting clinical progress has stimulated intense investigations in the broader family. Here, we discuss recent developments in small molecules targeting anti-apoptotic proteins and alternative approaches to targeting BCL-2 family interactions. These studies advance our understanding of the role of BCL-2 family proteins in physiology and disease, providing unique tools for dissecting these functions...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28732278/advances-of-small-molecule-targeting-of-kinases
#12
REVIEW
Norbert Berndt, Rezaul M Karim, Ernst Schönbrunn
Reversible protein phosphorylation regulates virtually all aspects of life in the cell. As a result, dysregulation of protein kinases, the enzymes responsible for transferring phosphate groups from ATP to proteins, are often the cause or consequence of many human diseases including cancer. Almost three dozen protein kinase inhibitors (PKIs) have been approved for clinical applications since 1995, the vast majority of them for the treatment of cancer. According to the NCI, there are more than 100 types of cancer...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28689146/chemical-modulators-for-epigenome-reader-domains-as-emerging-epigenetic-therapies-for-cancer-and-inflammation
#13
REVIEW
Nilesh Zaware, Ming-Ming Zhou
Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28689145/allosteric-regulation-of-epigenetic-modifying-enzymes
#14
REVIEW
Beth E Zucconi, Philip A Cole
Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28662389/recent-progress-in-developing-selective-inhibitors-of-protein-methyltransferases
#15
REVIEW
H Ümit Kaniskan, Jian Jin
Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histones as well as non-histone proteins, play a crucial role in diverse biological pathways and human diseases. In particular, PMTs have been recognized as major players in regulating gene expression and chromatin state. There has been an increasingly growing interest in these enzymes as potential therapeutic targets and over the past two years tremendous progress has been made in the discovery of selective, small molecule inhibitors of protein lysine and arginine methyltransferases...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28649012/small-molecule-probes-of-protein-aggregation
#16
REVIEW
Lydia M Young, Alison E Ashcroft, Sheena E Radford
Understanding the mechanisms of amyloid formation and toxicity remain major challenges. Although substantial progress has been made in the development of methods able to identify the species formed during self-assembly and to describe the kinetic mechanisms of aggregation, the structure(s) of non-native species, including potentially toxic oligomers, remain elusive. Moreover, how fibrils contribute to disease remains unclear. Here we review recent advances in the development of small molecules and other reagents that are helping to define the mechanisms of protein aggregation in molecular detail...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28645028/lipid-homeostasis-and-regulated-cell-death
#17
REVIEW
Eran Agmon, Brent R Stockwell
Modern lipidomics analysis paints a dynamic picture of membrane organizations, as changing and adapting lipid assemblies that play an active role in cellular function. This article highlights how the lipid composition of membranes determines specific organelle functions, how homeostatic mechanisms maintain these functions by regulating physical properties of membranes, and how cells disrupt lipid homeostasis to bring about regulated cell death (RCD). These are broad phenomena, and representative examples are reviewed here...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28628894/small-molecule-probes-for-cellular-death-machines
#18
REVIEW
Ying Li, Lihui Qian, Junying Yuan
The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28623730/quantitative-microscopy-based-on-single-molecule-fluorescence
#19
REVIEW
Seung-Ryoung Jung, Bryant S Fujimoto, Daniel T Chiu
Quantitative microscopy is needed to understand reactions or phenomena carried out by biological molecules such as enzymes, receptors, and membrane-localized proteins. Counting the biomolecules of interest in single organelles or cellular compartments is critical in these approaches. In this brief perspective, we focus on the development of quantitative fluorescence microscopies that measure the precise copy numbers of proteins in cellular organelles or purified samples. We introduce recent improvements in quantitative microscopies to overcome undercounting or overcounting errors in certain conditions...
August 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28609675/covalent-inhibitors-an-opportunity-for-rational-target-selectivity
#20
REVIEW
Roman Lagoutte, Remi Patouret, Nicolas Winssinger
There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine's thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine's amine can also be engaged covalently with a mild electrophile extends the potential of covalent inhibitors...
August 2017: Current Opinion in Chemical Biology
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