Thursday, April 17, 2014

Nature Chemical Biology Contents: May 2014 Volume 10 No 5 pp 319 - 406

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Nature Chemical Biology

TABLE OF CONTENTS

May 2014 Volume 10, Issue 5

Commentary
Research Highlights
News and Views
Perspective
Brief Communication
Articles

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Nature Structural & Molecular Biology 
FOCUS ON UBIQUITIN 

Ubiquitin and ubiquitin-like proteins have central roles in regulating cellular processes and homeostasis. This Focus examines our understanding of the ubiquitination reaction and the mechanisms by which ubiquitin and related modifications affect key cellular functions.

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Commentary

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Engineering synergy in biotechnology   pp319 - 322
Jens Nielsen, Martin Fussenegger, Jay Keasling, Sang Yup Lee, James C Liao et al.
doi:10.1038/nchembio.1519
Biotechnology is a central focus in efforts to provide sustainable solutions for the provision of fuels, chemicals and materials. On the basis of a recent open discussion, we summarize the development of this field, highlighting the distinct but complementary approaches provided by metabolic engineering and synthetic biology for the creation of efficient cell factories to convert biomass and other feedstocks to desired chemicals.

Research Highlights

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Metal regulation: Iron clad delivery | Immunology: Interfering with Interferon | Plant innate immunity: Tussling over tyrosine | Peptides: A synthetic step change | Cell biology: Just the two of us | Apoptosis: A channel off-target | Natural products: A painful discovery | Kinase regulation: Switching GSK3 off


News and Views

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Metabolism: Pathogens love the poison   pp326 - 327
Stéphane Ménage and Ina Attrée
doi:10.1038/nchembio.1505
Itaconate is a metabolite secreted by activated macrophages that inhibits pathogen growth. Some pathogens use itaconate degradation enzymes to promote their survival and infectivity, highlighting metabolic pathways to be considered in host-pathogen interactions.

Pluripotency: Citrullination unravels stem cells   pp327 - 328
Daniel J Slade, Venkataraman Subramanian and Paul R Thompson
doi:10.1038/nchembio.1504
Maintenance of the pluripotent stem cell state is regulated by the post-translational modification of histones. The discovery that citrullination of the linker histone H1 is critical to this process represents a new role for the protein arginine deiminases in development.

Labeling: Palladium brings proteins to life   pp328 - 330
Kun Qian and Yujun George Zheng
doi:10.1038/nchembio.1507
A bioorthogonal decaging strategy, mediated by small-molecule palladium compounds, can recover the lysine-dependent activity of cellular proteins. This activation technique could be generally applicable for controlling and probing function of a protein target in living cells.

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Perspective

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Rethinking biological activation of methane and conversion to liquid fuels   pp331 - 339
Chad A Haynes and Ramon Gonzalez
doi:10.1038/nchembio.1509
Methane is an energy resource that is currently being wasted through emissions, venting and flaring during petroleum extraction. Recent discoveries regarding the basis of enzyme function and microbial metabolism provide the foundation for new thinking about how to reclaim this resource through bioconversion.

Brief Communication

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Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides   pp340 - 342
Indran Mathavan, Séverine Zirah, Shahid Mehmood, Hassanul G Choudhury, Christophe Goulard et al.
doi:10.1038/nchembio.1499



Lasso peptides are antimicrobial bacterial peptides that hijack outer membrane siderophores to kill target cells. The structural and biochemical basis of antimicrobial lasso peptide MccJ25 binding to siderophore FhuA explains why these peptides have a narrow range of target species.

Articles

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Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39   pp343 - 349
Frederic Bassilana, Adam Carlson, Jennifer A DaSilva, Bianka Grosshans, Solange Vidal et al.
doi:10.1038/nchembio.1481



A new small-molecule inhibitor of the Hedgehog signaling pathway acts independently of Smoothened (Smo). Rather than acting through Smo, which is a GPCR-like protein of the pathway, the compound acts through the orphan GPCR GPR39, with the level of GPR39 activation correlating with Hh pathway inhibition.
Chemical compounds

Golgi sorting regulates organization and activity of GPI proteins at apical membranes   pp350 - 357
Simona Paladino, Stéphanie Lebreton, Simona Tivodar, Fabio Formiggini, Giulia Ossato et al.
doi:10.1038/nchembio.1495



High-resolution microscopy and biochemistry show that homoclusters of GPI-anchored proteins (GPI-APs) in the Golgi arrive at the apical membrane of polarized cells and then coalesce into larger heteroclusters. Therefore, sorting at the Golgi determines organization of GPI-APs at the plasma membrane.

G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation   pp358 - 364
Pierre Murat, Jie Zhong, Lea Lekieffre, Nathan P Cowieson, Jennifer L Clancy et al.
doi:10.1038/nchembio.1479



Biophysical analysis reveals that conserved G-rich sequences within the mRNAs of gammaherpesvirus genome maintenance proteins (GMPs) form G-quadruplexes (G4). Stabilization of mRNA G4 motifs represses GMP translation, whereas destabilization enhances translation, suggesting that these RNA elements are cis-acting translational regulators of proteins involved in viral latency.

Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark   pp365 - 370
Lunzhi Dai, Chao Peng, Emilie Montellier, Zhike Lu, Yue Chen et al.
doi:10.1038/nchembio.1497



Histone post-translational modifications are important regulators of chromatin structure and gene expression. Lysine 2-hydroxisobutyrylation sites, discovered by MS and validated by chemical synthesis, are found in active chromatin and associated with male germ cell differentiation.
Chemical compounds

Bacterial itaconate degradation promotes pathogenicity   pp371 - 377
Jahminy Sasikaran, Michał Ziemski, Piotr K Zadora, Angela Fleig and Ivan A Berg
doi:10.1038/nchembio.1482



Host cells respond to bacterial infection by producing itaconate, an inhibitor of bacterial metabolism, among other strategies. Biochemical characterization now defines genes known to be important for bacterial virulence as a new pathway that degrades itaconate into metabolic building blocks.

Reversible [4Fe-3S] cluster morphing in an O2-tolerant [NiFe] hydrogenase   pp378 - 385
Stefan Frielingsdorf, Johannes Fritsch, Andrea Schmidt, Mathias Hammer, Julia Löwenstein et al.
doi:10.1038/nchembio.1500



Certain oxygen-tolerant hydrogenases contain a unique [4Fe-3S] cluster near the catalytic site, but the role of this cofactor is not fully understood. Crystallographic, spectroscopic and computational data now provide evidence for redox-dependent transformations of this cluster, potentially explaining how specialized hydrogenases can safely reduce inhibitory O2.

Design of activated serine–containing catalytic triads with atomic-level accuracy   pp386 - 391
Sridharan Rajagopalan, Chu Wang, Kai Yu, Alexandre P Kuzin, Florian Richter et al.
doi:10.1038/nchembio.1498



De novo enzyme designs have generally tried to optimize multiple aspects of enzyme function simultaneously. Focusing only on positioning of active site residues to generate a nucleophilic serine as assessed by activity-based protein profiling now leads to a successful intermediate design.

Bioretrosynthetic construction of a didanosine biosynthetic pathway   pp392 - 399
William R Birmingham, Chrystal A Starbird, Timothy D Panosian, David P Nannemann, T M Iverson et al.
doi:10.1038/nchembio.1494



Bioretrosynthesis is meant to simplify construction of metabolic pathways by screening only for the final desired product. This approach, aided by protein design and crystallography, is now used to synthesize an antiretroviral nucleoside analog and surprisingly identifies a new enzyme function.
Chemical compounds

Amphotericin forms an extramembranous and fungicidal sterol sponge   pp400 - 406
Thomas M Anderson, Mary C Clay, Alexander G Cioffi, Katrina A Diaz, Grant S Hisao et al.
doi:10.1038/nchembio.1496



NMR structural data and biophysical and biological experiments show that the antifungal compound amphotericin is toxic because it acts as a sterol sponge by interacting with ergosterol on the fungal membrane and extracting it from within the membrane to the surface of the membrane.

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