Tuesday, November 21, 2017

Nature Chemical Biology Contents: December 2017, Volume 13 No 12 pp 1203 - 1286

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Nature Chemical Biology


December 2017 Volume 13, Issue 12

Research Highlights
News and Views

Web collection: Archaea and the tree of life

To mark 40 years of archaea research, Nature Reviews Microbiology presents a collection of articles from across Nature Research which explore the fundamental biology, evolution, metabolic versatility and ecological impact of archaea, and how the discovery of new species is reshaping the tree of life. 

Access the collection online — select content free to read for a limited time.

Recommend to library
Nature Collection: 2017 

Nobel Prize in Physiology or Medicine The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm. 

Access this collection free online 

Research Highlights


Nucleic acids: mRNAs get a TREAT | Peptide design: Hacking hemagglutinin | Host-pathogen interactions: A ubiquitin defense | Enzymology: I want my cluster back

News and Views


Cancer systems biology: Harnessing off-target effects   pp1204 - 1205
Gaye Saginc, Franziska Voellmy and Rune Linding
The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.

See also: Article by Kuenzi et al.

Genetic code expansion: Synthetases pick up the PACE   pp1205 - 1206
Jeffery M Tharp and Wenshe R Liu
Phage-assisted evolution can rapidly improve the efficiency and substrate specificity of orthogonal aminoacyl-tRNA synthetases. Furthermore, the crystal structure of the pyrrolysyl-tRNA synthetase N-terminal domain reveals the basis for these improvements and provides a structural rationale for orthogonality.

See also: Article by Bryson et al. | Article by Suzuki et al.

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Inhibition of USP10 induces degradation of oncogenic FLT3   pp1207 - 1215
Ellen L Weisberg, Nathan J Schauer, Jing Yang, Ilaria Lamberto, Laura Doherty et al.

An inhibitor of the deubiquitinase (DUB) USP10 regulates the degradation of oncogenic FLT3, thus defining USP10 as a DUB for FLT3 and providing a therapeutic approach for human acute myeloid leukemia in which FLT3 activation is dysregulated.
Chemical compounds

Regulation of nitric oxide signaling by formation of a distal receptor-ligand complex   pp1216 - 1221
Yirui Guo, Daniel L M Suess, Mark A Herzik Jr, Anthony T Iavarone, R David Britt et al.

Kinetic analysis and EPR spectroscopy measurements on a bacterial heme-nitric oxide/oxygen-binding (H-NOX) protein reveal that nitric oxide (NO) binds on the distal side of the heme cofactor under both limiting and excess NO conditions.

Polypharmacology-based ceritinib repurposing using integrated functional proteomics   pp1222 - 1231
Brent M Kuenzi, Lily L Remsing Rix, Paul A Stewart, Bin Fang, Fumi Kinose et al.

A systems chemical biology approach to characterize beneficial off-target effects revealed a polypharmacology mechanism for the multikinase inhibitor ceritinib and a repurposing opportunity through rational design of a synergistic drug combination.
Chemical compounds
See also: News and Views by Saginc et al.

The structure-energy landscape of NMDA receptor gating   pp1232 - 1238
Drew M Dolino, Sudeshna Chatterjee, David M MacLean, Charlotte Flatebo, Logan D C Bishop et al.

A linear gating mechanism links kinetically and structurally distinct closed and open states of NMDA receptors. During allosteric inhibition, agonist binding incudes uncoupling of structural changes from gating motions in the first transmembrane region.

Stendomycin selectively inhibits TIM23-dependent mitochondrial protein import   pp1239 - 1244
Ireos Filipuzzi, Janos Steffen, Mitchel Germain, Laetitia Goepfert, Michael A Conti et al.

The natural product stendomycin is a first-in-class inhibitor of the TIM23 mitochondrial translocon in yeast and mammalian cells that helped reveal that the TIM23 complex does not regulate transport of the autophagy regulator PINK1.

Changes in microtubule overlap length regulate kinesin-14-driven microtubule sliding   pp1245 - 1252
Marcus Braun, Zdenek Lansky, Agata Szuba, Friedrich W Schwarz, Aniruddha Mitra et al.

Microtubule sliding driven by kinesin-14 HSET is regulated by a feedback mechanism. When microtubules start sliding apart, HSET molecules are retained in the shortening overlap, which leads to an HSET-density-dependent decrease in sliding velocity.

Continuous directed evolution of aminoacyl-tRNA synthetases   pp1253 - 1260
David I Bryson, Chenguang Fan, Li-Tao Guo, Corwin Miller, Dieter Soll et al.

The use of phage-assisted continuous evolution (PACE) with both positive and negative selection enables the rapid development of orthogonal aminoacyl-tRNA synthetases with high activity and selectivity for noncanonical amino acids.
Chemical compounds
See also: News and Views by Tharp & Liu

Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase   pp1261 - 1266
Tateki Suzuki, Corwin Miller, Li-Tao Guo, Joanne M L Ho, David I Bryson et al.

The N-terminal domain structure of pyrrolysyl-tRNA synthetase (PylRS) reveals details of its tRNA specificity and facilitates the improvement of its selectivity for non-canonical amino acids by phage-assisted non-continuous evolution (PANCE).
Chemical compounds
See also: News and Views by Tharp & Liu

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase   pp1267 - 1273
Chia-Wei Hu, Matthew Worth, Dacheng Fan, Baobin Li, Hao Li et al.

N-Acetylglucosamine derivatives equipped with electrophilic groups and handles for subsequent chemical tagging are useful probes of substrate recognition by O-GlcNAc transferases and enable the capture of transient protein substrates of these enzymes.
Chemical compounds

A CRISPR screen identifies a pathway required for paraquat-induced cell death   pp1274 - 1279
Colleen R Reczek, Kıvanc Birsoy, Hyewon Kong, Inmaculada Martinez-Reyes, Tim Wang et al.

A positive-selection CRISPR screen with the pro-oxidant paraquat (PQ) uncovers three genes mediating PQ-induced cell death: POR is the source of PQ-mediated reactive oxygen species (ROS) generation, and ATP7A and SLC45A4 promote oxidant-dependent cell death.
Chemical compounds

Rational design of proteins that exchange on functional timescales   pp1280 - 1285
James A Davey, Adam M Damry, Natalie K Goto and Roberto A Chica

The development of a computational protein design method, meta-multistate design, enables the design and validation of protein variants termed DANCERs that spontaneously exchange between predicted conformational states on the millisecond timescale.



Errata: Functional annotation of chemical libraries across diverse biological processes   p1286
Jeff S Piotrowski, Sheena C Li, Raamesh Deshpande, Scott W Simpkins, Justin Nelson et al.

Errata: Functional annotation of chemical libraries across diverse biological processes   p1286
Jeff S Piotrowski, Sheena C Li, Raamesh Deshpande, Scott W Simpkins, Justin Nelson et al.

Focus issue on Mechanobiology 

Nature Reviews Molecular Cell Biology presents a focus issue highlighting the importance of mechanotransduction — the conversion of mechanical forces into biochemical signals — in morphogenesis, tissue regeneration and disease, including tumorigenesis. The articles discuss our understanding of how mechanical forces are transduced into the cell, including the nucleus, to regulate gene expression, and the therapeutic potential of modulating the mechanobiology of cells and tissues. 

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