Thursday, April 13, 2017

Nature Chemical Biology Contents: May 2017, Volume 13 No 5 pp 451 - 557

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Nature Chemical Biology

Focus on the origin of life

Nature Chemistry presents a Focus which explores the origins of RNA and its role in contemporary biological systems. The collection of articles reveal new insights into what early Earth might have looked like and how life first emerged.

Read the Focus

May 2017 Volume 13, Issue 5

Research Highlights
News and Views
Brief Communications

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September 27-29, 2017 | Seoul, Korea

Presented by: Institute for Basic Science | Institute of Genetics and Developmental Biology, CAS | Nature | Nature Biotechnology


Research Highlights


Optogenetics: Lighting up kinases | Bacterial Membranes: Tear down this wall | Intrinsic Disorder: Fuzzy fast feedback | Anti-Bacterials: Out-SMARting drug resistance

News and Views


Targeted protein degradation: You can glue it too!   pp452 - 453
Michal J Walczak, Georg Petzold and Nicolas H Thoma
Proteolysis-targeting chimera (PROTACs) are synthetic molecules that recruit neo-substrate proteins to a ubiquitin ligase for ubiquitination and subsequent degradation. Structural insight into the VHL-MZ1-BRD4 complex reveals how the rationally designed MZ1-PROTAC molecule mediates degradation of an unnatural protein substrate.

See also: Article by Gadd et al.

Microbiology: A new language for small talk   pp453 - 454
Yi-Ming Shi and Helge B Bode
A new signal-receptor pair involved in regulating biofilm formation and virulence was detected in Vibrio cholerae. Both the signal and the transcription factor belong to common classes of natural products and receptor proteins, suggesting widespread importance of related systems in nature.

See also: Article by Papenfort et al.

Nature Chemical Biology
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The chemical basis for electrical signaling   pp455 - 463
William A Catterall, Goragot Wisedchaisri and Ning Zheng

A highlight of the knowledge derived in large part from structural work on physical motions and chemical interactions involved in voltage sensing, pore opening, ion conductance and selectivity, and voltage-dependent inactivation mechanisms of the voltage-gated channels NaV and CaV.

Brief Communications


A fully automated flow-based approach for accelerated peptide synthesis   pp464 - 466
Alexander J Mijalis, Dale A Thomas III, Mark D Simon, Andrea Adamo, Ryan Beaumont et al.

An automated method for solid-phase polypeptide synthesis capitalizes on rapid amide bond formation to enable the production of multiple traditionally difficult-to-synthesize sequences with both high yield and high purity.

Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids   pp467 - 469
Shasha Li, Andrew N Lowell, Sean A Newmister, Fengan Yu, Robert M Williams et al.

Characterization of a family of Stigonematales (Stig) cyclases that catalyze stereoselective intramolecular C-C bond formation reveals the enzymatic origins of the complex stereochemical patterns in hapalindole and fischerindole alkaloids.
Chemical compounds

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A new genome-mining tool redefines the lasso peptide biosynthetic landscape   pp470 - 478
Jonathan I Tietz, Christopher J Schwalen, Parth S Patel, Tucker Maxson, Patricia M Blair et al.

RODEO, an algorithm developed for RiPP natural product discovery, was applied to map out the gene clusters that encode and tailor lasso peptides and led to the identification and characterization of several new lasso peptide topologies.
Chemical compounds

The Arabidopsis O-fucosyltransferase SPINDLY activates nuclear growth repressor DELLA   pp479 - 485
Rodolfo Zentella, Ning Sui, Benjamin Barnhill, Wen-Ping Hsieh, Jianhong Hu et al.

Mass spectrometry analysis combined with in vitro assays reveals that SPINDLY is an O-fucosyltransferase that modifies the growth repressor DELLA and consequently enhances its activity to regulate transcription of target genes.

Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11   pp486 - 493
Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L Mackinnon, Christian Perez et al.

Two screening approaches converge on capzimin, a first-in-class inhibitor of the Rpn11 protease component of the 19S proteasome. Capzimin stabilizes polyubiquitinated substrates, induces the unfolded protein response, and blocks proliferation of cancer cells.
Chemical compounds

L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH   pp494 - 500
Andrew M Intlekofer, Bo Wang, Hui Liu, Hardik Shah, Carlos Carmona-Fontaine et al.

Acidification enhances lactate dehydrogenase- and malate dehydrogenase-mediated promiscuous production of L-2-hydroxyglutarate (L-2HG) from α-ketoglutarate and stabilizes HIF-1α levels.

Total RNA-seq to identify pharmacological effects on specific stages of mRNA synthesis   pp501 - 507
Sarah A Boswell, Andrew Snavely, Heather M Landry, L Stirling Churchman, Jesse M Gray et al.

The application of strand-specific total RNA sequencing combined with metagene analysis enables detection of small-molecule-mediated effects on transcription initiation, elongation or RNA processing, and reveals that isoginkgetin blocks transcriptional elongation.

The structure of a nucleolytic ribozyme that employs a catalytic metal ion   pp508 - 513
Yijin Liu, Timothy J Wilson and David M J Lilley

The structure of the TS (formerly twister sister) ribozyme reveals details about its catalytic mechanism of nucleolytic self-cleavage using a hydrated magnesium ion, and illustrates key differences between it and the related twister ribozyme.

Structural basis of PROTAC cooperative recognition for selective protein degradation   pp514 - 521
Morgan S Gadd, Andrea Testa, Xavier Lucas, Kwok-Ho Chan, Wenzhang Chen et al.

The description of the crystal structure of the Brd4 PROTAC compound MZ1 in complex with the human E3 ubiquitin ligase VHL and the Brd4 bromodomain shines new light onto how PROTACs work and enables design of degraders with increased selectivity for Brd4.
Chemical compounds
See also: News and Views by Walczak et al.

The Rrp4-exosome complex recruits and channels substrate RNA by a unique mechanism   pp522 - 528
Milos A Cvetkovic, Jan Philip Wurm, Maxime J Audin, Stefan Schutz and Remco Sprangers

A methyl-TROSY NMR approach provides a detailed model for how the archaeal exosome cap recruits multiple RNA substrates and channels them one by one into the catalytic barrel for degradation.

In silico design of novel probes for the atypical opioid receptor MRGPRX2   pp529 - 536
Katherine Lansu, Joel Karpiak, Jing Liu, Xi-Ping Huang, John D McCorvy et al.

High-throughput screening identifies opioid compounds and prodynorphin-derived peptide agonists of the G-protein-coupled receptor MRGPRX2 and informs a homology model that is used for in silico screening to find a small-molecule probe that provokes degranulation in mast cells, which express this receptor.
Chemical compounds

Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges   pp537 - 543
Vinayak Agarwal, Jessica M Blanton, Sheila Podell, Arnaud Taton, Michelle A Schorn et al.

Metagenomic analysis and functional characterization of biosynthetic genes uncovers the basis for widespread polybrominated diphenyl ether biosynthesis in cyanobacterial endosymbionts of marine Dysideidae sponges.
Chemical compounds

The direct role of selenocysteine in [NiFeSe] hydrogenase maturation and catalysis   pp544 - 550
Marta C Marques, Cristina Tapia, Oscar Gutierrez-Sanz, Ana Raquel Ramos, Kimberly L Keller et al.

Structural and functional characterization of a [NiFeSe] hydrogenase and its conversion to the [NiFe] type by mutagenesis indicate roles for the selenocysteine residue in metal incorporation, catalysis, and protection against oxidative deactivation.

A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation   pp551 - 557
Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost et al.

A new autoinducer-receptor pair, 3,5-dimethylpyrazin-2-ol (DPO)-VqmA, acts in parallel to canonical Vibrio cholerae quorum-sensing pathways. Downstream of VqmA is the small RNA target VqmR, which, like DPO, represses genes required for biofilm formation and toxin production.
Chemical compounds
See also: News and Views by Shi & Bode

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