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Nature Chemical Biology Contents: June 2016, Volume 12 No 6 pp 381 - 466

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TABLE OF CONTENTS

June 2016 Volume 12, Issue 6

Editorial
Commentary
Research Highlights
News and Views
Brief Communications
Articles
Erratum
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Editorial

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Lighting the way   p381
doi:10.1038/nchembio.2101
The innovation and optimization of optogenetic tools are providing new insights into biological and cellular processes with unparalleled spatiotemporal resolution.

Commentary

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Designing convergent chemistry curricula   pp382 - 386
Louise K Charkoudian, Nicole S Sampson, Krishna Kumar and Joshua A Kritzer
doi:10.1038/nchembio.2090
Scientific convergence is a common theme of modern research, but undergraduate chemistry is commonly taught as an isolated discipline. Here we discuss curricular updates at three different institutions that are independently seeking to increase convergence in introductory chemistry courses.

Research Highlights

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Genomics: A Tribe for RNA | Gene expression: Means to an end | Protein evolution: Polymerase's new language | Host-microbe interactions: Inflammation sop-up

News and Views

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Proteostasis: Chaperoning for hearing loss   pp388 - 389
Gergely L Lukacs
doi:10.1038/nchembio.2091
A small molecule has been identified that can mitigate the progression of an inherited form of deafness in transgenic mice by stabilizing mutant clarin-1, an essential component of a multimolecular complex of the mechanotransduction apparatus of hair cells in the inner ear.

See also: Article by Alagramam et al.

Cancer metabolism: Addicted to serine   pp389 - 390
Christian Frezza
doi:10.1038/nchembio.2086
Phosphoglycerate dehydrogenase (PHGDH) is an enzyme of serine biosynthesis overexpressed in various types of cancer. A new series of PHGDH inhibitors selectively block proliferation of PHGDH-dependent cancer cells and reveal an unexpected role of serine biosynthesis in coordinating one-carbon metabolism.

See also: Article by Pacold et al.

Metalloproteins: Mapping elusive electron density   pp391 - 392
Louis Noodleman
doi:10.1038/nchembio.2088
Iron-sulfur metalloproteins are critical for electron transfer in bacterial metabolism, but most crystal structures are insufficient for their in-depth study. Now, acquisition of an iron-sulfur protein structure at ultra-high resolution enables detailed visualization of its electron distribution.

Chemical Biology
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Brief Communications

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A synthetic biochemistry module for production of bio-based chemicals from glucose   pp393 - 395
Paul H Opgenorth, Tyler P Korman and James U Bowie
doi:10.1038/nchembio.2062



A synthetic biochemistry approach optimizes a glucose breakdown pathway to produce acetyl-CoA as a building block for polyhydroxybutyrate bioplastic production in the test tube.

The Taf14 YEATS domain is a reader of histone crotonylation   pp396 - 398
Forest H Andrews, Stephen A Shinsky, Erin K Shanle, Joseph B Bridgers, Anneliese Gest et al.
doi:10.1038/nchembio.2065



Crotonylated lysine residues within histones are linked to transcriptional activation in a process involving histone mark 'reader' proteins. Crystallographic analysis of the YEATS domain of the Taf14 protein reveals a mode of crotonylated histone mark recognition via a π-sandwich motif.

Light-induced nuclear export reveals rapid dynamics of epigenetic modifications   pp399 - 401
Hayretin Yumerefendi, Andrew Michael Lerner, Seth Parker Zimmerman, Klaus Hahn, James E Bear et al.
doi:10.1038/nchembio.2068



The attachment of a nuclear export sequence to the blue light-sensitive LOV2 domain mediates rapid and reversible protein export of the ubiquitin ligase Bre1 with light exposure, resulting in changes in histone ubiquitylation and methylation.

Articles

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Raft-based interactions of gangliosides with a GPI-anchored receptor   pp402 - 410
Naoko Komura, Kenichi G N Suzuki, Hiromune Ando, Miku Konishi, Machi Koikeda et al.
doi:10.1038/nchembio.2059



Monitoring new fluorescent ganglioside analogs at a single-molecule level suggests that gangliosides associate dynamically with GPI-anchored protein monomers, transient homodimer rafts, and clustered signaling rafts in a cholesterol-dependent manner.
Chemical compounds

Decoding Polo-like kinase 1 signaling along the kinetochore-centromere axis   pp411 - 418
Robert F Lera, Gregory K Potts, Aussie Suzuki, James M Johnson, Edward D Salmon et al.
doi:10.1038/nchembio.2060



A chemical genetic approach to localize human Polo-like kinase 1 (Plk1) to distinct regions along the kinetochore-centromere axis combined with phosphoproteomic analysis reveals the presence of distinct Plk1 pools to mediate chromosomal segregation.

Plant-like biosynthesis of isoquinoline alkaloids in Aspergillus fumigatus   pp419 - 424
Joshua A Baccile, Joseph E Spraker, Henry H Le, Eileen Brandenburger, Christian Gomez et al.
doi:10.1038/nchembio.2061



Analysis of orphan nonribosomal peptide synthetase-like gene clusters from Aspergillus fumigatus identified a gene cluster responsible for the biosynthesis of fumisoquin isoquinoline alkaloids by amino acid condensation and subsequent tailoring steps reminiscent of plant biosynthetic pathways.
Chemical compounds

Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase   pp425 - 430
Amir Taslimi, Brian Zoltowski, Jose G Miranda, Gopal P Pathak, Robert M Hughes et al.
doi:10.1038/nchembio.2063



Identification of minimal functional CRY2-CIB1 domains and mutations that increased CRY2 photocycle lifetimes combined with the development of an improved photoactivable Cre recombinase enables efficient gene editing.

Optogenetic oligomerization of Rab GTPases regulates intracellular membrane trafficking   pp431 - 436
Mai Khanh Nguyen, Cha Yeon Kim, Jin Man Kim, Byung Ouk Park, Sangkyu Lee et al.
doi:10.1038/nchembio.2064



An optogenetic approach using the CRY2-CIB1 heterodimerization system results in light-mediated cross-linking and aggregation of different Rab GTPases, disrupting membrane and endosomal trafficking in various cell types.

Real-time monitoring of basal H2O2 levels with peroxiredoxin-based probes   pp437 - 443
Bruce Morgan, Koen Van Laer, Theresa N E Owusu, Daria Ezerina, Daniel Pastor-Flores et al.
doi:10.1038/nchembio.2067



A fluorescent sensor combining a mutated form of the 2-Cys peroxiredoxin Tsa2 unable to undergo thioredoxin-mediated reduction with a redox-sensitive GFP protein allows real-time detection of baseline hydrogen peroxide levels in yeast cells.

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III   pp444 - 451
Kumar N Alagramam, Suhasini R Gopal, Ruishuang Geng, Daniel H-C Chen, Ina Nemet et al.
doi:10.1038/nchembio.2069



A small molecule identified from high-throughput screening and optimization specifically stabilizes a disease-linked CLRN1 protein, delivering it to its site of action at the plasma membrane and preserving hearing in a new mouse model for Usher syndrome type III.
Chemical compounds
See also: News and Views by Lukacs

A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate   pp452 - 458
Michael E Pacold, Kyle R Brimacombe, Sze Ham Chan, Jason M Rohde, Caroline A Lewis et al.
doi:10.1038/nchembio.2070



A quantitative high-throughput screen identified an inhibitor of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine synthesis. This inhibitor limits one-carbon unit availability for nucleotide synthesis.
Chemical compounds
See also: News and Views by Frezza

Click-EM for imaging metabolically tagged nonprotein biomolecules   pp459 - 465
John T Ngo, Stephen R Adams, Thomas J Deerinck, Daniela Boassa, Frances Rodriguez-Rivera et al.
doi:10.1038/nchembio.2076



A new technique called click-EM uses singlet oxygen-generating fluorescent dyes and correlated light microscopy and EM to metabolically label and visualize nucleic acids and lipids at high resolution in cultured neurons and cells.

Erratum

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Erratum: Chemoproteomic profiling of host and pathogen enzymes active in cholera   p466
Stavroula K Hatzios, Soren Abel, Julianne Martell, Troy Hubbard, Jumpei Sasabe et al.
doi:10.1038/nchembio0616-466

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