Tuesday, January 19, 2016

Nature Chemical Biology Contents: February 2016, Volume 12 No 2 pp 53 - 123

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Nature Chemical Biology

TABLE OF CONTENTS

February 2016 Volume 12, Issue 2

Research Highlights
News and Views
Perspective
Brief Communications
Articles

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Research Highlights

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Neurobiology: Tracking the scent | Antivirals: Alphaviruses feel the STING | Oxidative damage: A pathway to stress | Metalloenzymes: Getting the gold


News and Views

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Protein engineering: Beating the odds   pp54 - 55
Uwe T Bornscheuer
doi:10.1038/nchembio.1989
Recently developed advanced microfluidics-based systems have outperformed known screening tools with respect to throughput, flexibility, sensitivity and tricks for hit recovery. This has enabled the discovery of novel and improved proteins from random mutagenesis libraries or metagenome-based sources.

See also: Article by Chen et al.

Synthetic biology: Building genetic containment   pp55 - 56
Karmella A Haynes
doi:10.1038/nchembio.2004
Since the 1980s, scientists have worked on designing genetic codes to reinforce containment and control of genetically engineered microbes. New mechanistic studies of "deadman" and "passcode" gene circuits provide a flexible platform to build new safety switches.

Chemical probes: The many genes of drug mechanism   pp57 - 58
Adam C Palmer
doi:10.1038/nchembio.2010
A small molecule's biological activity in a cell depends on the actions of many gene products. Correlations between basal gene expression and compound sensitivity across hundreds of human cell lines reveal a broad view of cellular mechanisms of action.

Protein aggregation: A rescue by chaperones   pp58 - 59
Joost Schymkowitz and Frederic Rousseau
doi:10.1038/nchembio.2006
Protein aggregation is associated with more than 50 human pathologies, including prevalent conditions such as Alzheimer's and Parkinson's diseases. A phenotypic screen in Escherichia coli associating antibiotic resistance with the inhibition of protein aggregation now allows screening for chemical inhibitors of protein aggregation in a simple, fast and inexpensive manner.

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Perspective

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Fatty acylation of Wnt proteins   pp60 - 69
Aaron H Nile and Rami N Hannoush
doi:10.1038/nchembio.2005



This Perspective discusses recent advances in understanding the biochemistry, enzymology and cell biology of Wnt fatty acylation and its effects on signaling and cancer.

Brief Communications

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Photo-lysine captures proteins that bind lysine post-translational modifications   pp70 - 72
Tangpo Yang, Xiao-Meng Li, Xiucong Bao, Yi Man Eva Fung and Xiang David Li
doi:10.1038/nchembio.1990



Post-translational modifications (PTMs) of lysine side chains are important mediators of protein-protein interactions, particularly in chromatin. Photo-lysine, a diazirine analog of lysine, provides a tool to covalently capture proteins that bind lysine and its PTMs.
Chemical compounds

A nitrous acid biosynthetic pathway for diazo group formation in bacteria   pp73 - 75
Yoshinori Sugai, Yohei Katsuyama and Yasuo Ohnishi
doi:10.1038/nchembio.1991



Cremeomycin is a diazo-containing natural product. Assignment of the functions of individual enzymes in the gene cluster for cremeomycin biosynthesis reveals a pathway by which Streptomyces cremeus converts L-aspartic acid into the nitrous acid needed for diazotization chemistry.
Chemical compounds

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Articles

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High-throughput analysis and protein engineering using microcapillary arrays   pp76 - 81
Bob Chen, Sungwon Lim, Arvind Kannan, Spencer C Alford, Fanny Sunden et al.
doi:10.1038/nchembio.1978



A new technology platform called μSCALE combines the use of a microcapillary array with laser-based extraction to enable high-throughput biochemical and biophysical analysis and isolation of protein variants for protein-engineering applications.

See also: News and Views by Bornscheuer

'Deadman' and 'Passcode' microbial kill switches for bacterial containment   pp82 - 86
Clement T Y Chan, Jeong Wook Lee, D Ewen Cameron, Caleb J Bashor and James J Collins
doi:10.1038/nchembio.1979



Synthetic biology has expanded the availability of engineered bacterial systems for diverse applications and is now developing safeguards for their effective and secure use. The report of two synthetic gene circuit 'kill switches' provides new biocontainment mechanisms for engineered Escherichia coli.

See also: News and Views by Haynes

Molecular mechanism of respiratory syncytial virus fusion inhibitors   pp87 - 93
Michael B Battles, Johannes P Langedijk, Polina Furmanova-Hollenstein, Supranee Chaiwatpongsakorn, Heather M Costello et al.
doi:10.1038/nchembio.1982



The binding of small-molecule inhibitors of the RSV F glycoprotein in a central cavity in the prefusion conformation stabilizes this conformation and blocks the conformational changes required for fusion with host membranes.

An in vivo platform for identifying inhibitors of protein aggregation   pp94 - 101
Janet C Saunders, Lydia M Young, Rachel A Mahood, Matthew P Jackson, Charlotte H Revill et al.
doi:10.1038/nchembio.1988



Applying an in vivo bacterial-based system for monitoring the influence of small molecules on the aggregation of model amyloid proteins expressed in the periplasm identified dopamine as a new inhibitor of hIAPP aggregation, a protein involved in type 2 diabetes mellitus.

Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics   pp102 - 108
Luc de Waal, Timothy A Lewis, Matthew G Rees, Aviad Tsherniak, Xiaoyun Wu et al.
doi:10.1038/nchembio.1984



Phenotypic screening in cancer cell lines combined with chemogenomics analysis reveals a correlation between DNMDP sensitivity and increased PDE3A expression. DNMDP binding to PDE3A induces a switch resulting in interactions with SLFN12 and SIRT7.
Chemical compounds

Correlating chemical sensitivity and basal gene expression reveals mechanism of action   pp109 - 116
Matthew G Rees, Brinton Seashore-Ludlow, Jaime H Cheah, Drew J Adams, Edmund V Price et al.
doi:10.1038/nchembio.1986



A computational tool provides a systematic approach to determine the mechanisms of action of small molecules by examining correlations between basal gene expression and small-molecule sensitivity in cancer cell lines.

Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway   pp117 - 123
Tamjeed Saleh, Wojciech Jankowski, Ganapathy Sriram, Paolo Rossi, Shreyas Shah et al.
doi:10.1038/nchembio.1981



Cyclophilin A binds a proline motif in human CrkII, preventing phosphorylation by Abl and EGFR. Decreased CrkII phosphorylation ensures interactions with the focal adhesion proteins paxillin and p130CAS to stimulate cellular migration.

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