Nature Chemical Biology Contents: June 2014 Volume 10 No 6 pp 407 - 482

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TABLE OF CONTENTS June 2014 Volume 10, Issue 6 Editorial Research Highlights News and Views Review Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Special on Synthetic Biology From Nature, Nature Methods & Nature Reviews Microbiology Since its debut almost 15 years ago, synthetic biology has evolved into a vibrant and productive field. This Nature special charts the progress of this multidisciplinary field through reports, reviews and commentaries from Nature, Nature Methods and Nature Reviews Microbiology.  Click here to access this Special!   Editorial Top Wish you were here   p407 doi:10.1038/nchembio.1546 Young scientists should use conference time to maximize exposure of and get feedback on their work and to establish contacts within their scientific community. Research Highlights Top Chemotaxis: Small molecule GPS | Non-coding RNA: Lost on translation | Cell walls: Designed for deconstruction | Nanotechnology: Receptors navigate an array | Membrane transport: A phospholipid path | Diabetes: Relayed by a kiss | Synthesis: A plethora of polyenes | Cancer therapeutics: Cleaning the nucleotide pool News and Views Top Glycobiology: Drifting toward polymer perfection   pp410 - 411 Karen J Colley doi:10.1038/nchembio.1506 The addition of polysialic acid to proteins and cells is emerging as a promising therapeutic strategy. Polysialyltransferases synthesize polymers of widely varying lengths not optimal for therapeutic reagents, but the development of enzyme variants using neutral genetic drift offers a new way to overcome this problem. See also: Article by Keys et al. Antimicrobial mechanisms: A sponge against fungal infections   pp411 - 412 Karl Lohner doi:10.1038/nchembio.1518 The finding that the antifungal activity of amphotericin B is primarily due to its ability to extract ergosterol from fungal membranes suggests a new rationale for drug design, which should lead to advanced treatments, particularly for invasive fungal infections. See also: Article by Anderson et al. Structural biology: A 'funny' cyclic dinucleotide receptor   pp413 - 414 Yoni Haitin doi:10.1038/nchembio.1530 Deciphering the molecular basis of HCN channel regulation by cGMP leads to the serendipitous discovery of cyclic dinucleotides as potent inhibitors of If current in the heart. See also: Article by Lolicato et al. Plant signaling: Abscisic acid receptor hole-in-one   pp414 - 415 Ken-ichiro Hayashi and Toshinori Kinoshita doi:10.1038/nchembio.1529 The phytohormone abscisic acid (ABA) has a central role in adaptive responses of plants to abiotic stress. A new ABA antagonist offers a promising tool to study ABA signaling and adaptation to abiotic stress in diverse plants, including crops. See also: Article by Takeuchi et al. Chemical Biology JOBS of the week Postdoctoral Positions in Organic Synthesis / Chemical Biology at the University of Pittsburgh Kabirul Islam Faculty Positions State Key Laboratory of Medicinal Chemical Biology (Nankai University) Research Associate The Scripps Research Institute - Scripps Florida More Science jobs from Chemical Biology EVENT Molecular Switches 24 September 2014 Prien, Germany More science events from Review Top Gut microbiota-generated metabolites in animal health and disease   pp416 - 424 Won-Jae Lee and Koji Hase doi:10.1038/nchembio.1535 Understanding the mechanisms by which gut metabolites impact host physiology should help understand a variety of disease associated with gut-microbiota dysbiosis. A review of this microbial impact in both invertebrate and vertebrate highlights roles in energy harvest, pathogen resistance and the development of allergic and neurological disorders. Brief Communications Top A multifunctional enzyme is involved in bacterial ether lipid biosynthesis   pp425 - 427 Wolfram Lorenzen, Tilman Ahrendt, Kenan A J Bozhüyük and Helge B Bode doi:10.1038/nchembio.1526 Ether lipids are found in both mammals and bacteria, but only the mammalian biosynthesis pathway is known. Bioinformatic, biochemical and genetic evidence now locate the bacterial pathway within a multigene cluster that includes the four-domain, PKS-like ElbD. Dynamics and hydration explain failed functional transformation in dehalogenase design   pp428 - 430 Jan Sykora, Jan Brezovsky, Tana Koudelakova, Maryna Lahoda, Andrea Fortova et al. doi:10.1038/nchembio.1502 The transplantation of residues from a selective to a nonselective haloalkane dehalogenase yields the correct active site geometry but not function. Computational and biophysical results explain this disparity, showing that the dynamics and hydration of the engineered protein match its parent, not its target. Articles Top The role of distant mutations and allosteric regulation on LovD active site dynamics   pp431 - 436 Gonzalo Jiménez-Osés, Sílvia Osuna, Xue Gao, Michael R Sawaya, Lynne Gilson et al. doi:10.1038/nchembio.1503 Directed evolution of the final enzyme in the lovastatin biosynthetic pathway yields a variant with 29 mutations that does not require a carrier protein and displays altered dynamics of the catalytic residues, spending more time in the catalytically active conformation. Engineering the product profile of a polysialyltransferase   pp437 - 442 Timothy G Keys, Hazel L S Fuchs, Jörg Ehrit, Jürgen Alves, Friedrich Freiberger et al. doi:10.1038/nchembio.1501 Functional assessments and applications of polysaccharides are hampered by broad product distributions. Neutral drift libraries now identify specific amino acids and binding sites that determine product outcome in a polysialyltransferase, allowing the preparation of glycan chains with defined lengths. See also: News and Views by Colley Pharmacological chaperones stabilize retromer to limit APP processing   pp443 - 449 Vincent J Mecozzi, Diego E Berman, Sabrina Simoes, Chris Vetanovetz, Mehraj R Awal et al. doi:10.1038/nchembio.1508 In silico screening identifies a small molecule that stabilizes the interaction between retromer components Vps35 and Vps29. The compound increases traffic of APP away from the endosomal compartment to limit generation of the Aβ peptides involved in Alzheimer's disease pathology. Chemical compounds Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase   pp450 - 456 Estrella Luna, Marieke van Hulten, Yuhua Zhang, Oliver Berkowitz, Ana López et al. doi:10.1038/nchembio.1520 β-Aminobutyric acid (BABA) is a small-molecule activator of plant disease resistance. Binding of (R)-BABA to IBI1—an aspartyl-tRNA synthetase (AspRS)—primes noncanonical defense pathways, resulting in broad-spectrum disease resistance. Ligand binding also blocks AspRS activity, leading to accumulation of aspartic acid and uncharged tRNA, which activate a second plant stress response. Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness   pp457 - 462 Marco Lolicato, Annalisa Bucchi, Cristina Arrigoni, Stefano Zucca, Marco Nardini et al. doi:10.1038/nchembio.1521 A cyclic dinucleotide binds to a ‘C-linker pocket’ of the HCN4 ion channel, a site that is distinct from the cyclic nucleotide binding site used for channel regulation. A small molecule found to interact with the C-linker pocket can antagonize cAMP regulation of the channel. Chemical compounds See also: News and Views by Haitin The voltage-gated sodium channel TPC1 confers endolysosomal excitability   pp463 - 469 Chunlei Cang, Biruk Bekele and Dejian Ren doi:10.1038/nchembio.1522 Endosomes and lysosomes are electrically excitable, and this is conferred by a new family of atypical voltage-gated sodium channels, lysoNaVs, formed by TPC1, which has similar mechanisms for gating as canonical voltage-gated channels and is sensitive to pH, appropriate for its localization in acidic compartments. Microbial glycan microarrays define key features of host-microbial interactions   pp470 - 476 Sean R Stowell, Connie M Arthur, Ryan McBride, Oren Berger, Nahid Razi et al. doi:10.1038/nchembio.1525 An array of approximately 300 different carbohydrate structures from select gut bacteria was generated and probed with mouse and rabbit IgG samples. The binding results indicate that galectins 3, 4 and 8 of the innate immune system can recognize certain microbes only if they express self-like antigens. Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions   pp477 - 482 Jun Takeuchi, Masanori Okamoto, Tomonori Akiyama, Takuya Muto, Shunsuke Yajima et al. doi:10.1038/nchembio.1524 Abscisic acid (ABA), a small-molecule hormone that regulates stress responses in plants, initiates signaling by nucleating ABA receptor–PP2C interactions. A structure-guided approach has produced a class of 3′-S-alkylated ABA derivatives that prevent PP2C binding to ABA receptors by blocking a solvent-exposed channel. Chemical compounds See also: News and Views by Hayashi & Kinoshita Top Advertisement Nature Structural & Molecular Biology  FOCUS ON UBIQUITIN  Ubiquitin and ubiquitin-like proteins have central roles in regulating cellular processes and homeostasis. 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