Monday, June 17, 2013

Nature Chemical Biology Contents: July 2013 Volume 9 Number 7, pp 408 - 466

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Frontiers in Chemical Biology, a speciality section of Frontiers in Chemistry, offers a peer-reviewed and open access option to chemists, biologists and other researchers that develop and apply chemical tools to investigate biological systems and processes
 
TABLE OF CONTENTS

July 2013 Volume 9, Issue 7

Research Highlights
News and Views
Articles
Erratum
Corrigenda

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Have you read this highly downloaded original article recently published in Cell Research

Genome editing with RNA-guided Cas9 nuclease in Zebrafish embryos
Nannan Chang, Changhong Sun, Lu Gao, Dan Zhu, Xiufei Xu, Xiaojun Zhu, Jing-Wei Xiong & Jianzhong Jeff Xi 

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Research Highlights

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Biosynthesis: Set me free | Cell biology: Viruses get an ESCRT | Microbiology: I'm beginning to see the light | Cell death: NonALKylating activity | tRNA Modifications: A structured answer | Protein folding: Retaining clients | Protein folding: Sweetening the deal | Microbiology: A lipid under stress


News and Views

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Protein dynamics: Catch them if you can   pp410 - 411
Gianluigi Veglia
doi:10.1038/nchembio.1258
NMR analysis of the conformational energy landscape of the catabolite activator protein suggests that allosteric inhibition can be achieved by blocking access to elusive high-energy states of proteins.

See also: Article by Tzeng & Kalodimos

Post-translational modifications: Panning for phosphohistidine   pp411 - 412
Matthew J Piggott and Paul V Attwood
doi:10.1038/nchembio.1273
Elusive pan-phosphohistidine (pHis) antibodies have been generated using a hydrolytically stable triazolyl-phosphonate hapten, promising to substantially accelerate efforts to better understand the role of pHis in biology.

See also: Article by Kee et al.

Structural biology: FaPy lesions and DNA mutations   pp412 - 414
Kent S Gates
doi:10.1038/nchembio.1274
Formamidopyrimidine residues are damaged purines that retain the same Watson-Crick hydrogen-bonding face found in the parent nucleobase, yet these lesions are mutagenic. Crystallographic evidence suggests molecular mechanisms by which these lesions 'mispair' to generate mutations during DNA replication.

See also: Article by Gehrke et al.

Signaling: Sifting at the ciliary base   pp414 - 415
Prachee Avasthi
doi:10.1038/nchembio.1272
Transduction of extracellular signals by cilia requires regulated entry of pathway components. A new study uses chemical dimerization to induce diffusion and identifies size-dependent soluble diffusion rates consistent with a sieve-like barrier with 8-nm pore radii at the ciliary base.

See also: Article by Lin et al.

Chemical Biology
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Articles

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A pan-specific antibody for direct detection of protein histidine phosphorylation   pp416 - 421
Jung-Min Kee, Rob C Oslund, David H Perlman and Tom W Muir
doi:10.1038/nchembio.1259



Studies of histidine phosphorylation have been limited owing to a lack of appropriate tools. The synthesis of a stable phosphohistidine mimic now leads to a pan antibody, enabling detection and further functional investigations of this little-known post-translational modification.
Chemical compounds
See also: News and Views by Piggott & Attwood

A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr    pp422 - 427
Tyler L Grove, Jovan Livada, Erica L Schwalm, Michael T Green, Squire J Booker and Alexey Silakov
doi:10.1038/nchembio.1251



The radical SAM enzyme Cfr catalyzes methylation of a ribosomal adenosine, causing broad antibiotic resistance. EPR and ENDOR techniques now provide direct evidence for the proposed enzymatic mechanism by detecting a central crosslinked intermediate in which a radical is located on the nucleotide.

Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization   pp428 - 436
Hugo Lavoie, Neroshan Thevakumaran, Gwenaëlle Gavory, John J Li, Abbas Padeganeh, Sébastien Guiral, Jean Duchaine, Daniel Y L Mao, Michel Bouvier, Frank Sicheri and Marc Therrien
doi:10.1038/nchembio.1257



ATP-competitive RAF kinase inhibitors stabilize a closed and rigid active conformation of the RAF kinase domain, which leads to RAF dimerization and allosteric activation of the inhibitor-free protomer.

Chemically inducible diffusion trap at cilia reveals molecular sieve–like barrier   pp437 - 443
Yu-Chun Lin, Pawel Niewiadomski, Benjamin Lin, Hideki Nakamura, Siew Cheng Phua, John Jiao, Andre Levchenko, Takafumi Inoue, Rajat Rohatgi and Takanari Inoue
doi:10.1038/nchembio.1252



Chemically inducible diffusion trap at cilia (CIDTc), a method to trap proteins in the cilia, was applied to study the kinetics of protein accumulation and reveal a molecular sieve at the ciliary base. CIDTc can also be applied to study signaling pathways in the cilia.

See also: News and Views by Avasthi

Mechanism-based corrector combination restores ΔF508-CFTR folding and function   pp444 - 454
Tsukasa Okiyoneda, Guido Veit, Johanna F Dekkers, Miklos Bagdany, Naoto Soya, Haijin Xu, Ariel Roldan, Alan S Verkman, Mark Kurth, Agnes Simon, Tamas Hegedus, Jeffrey M Beekman and Gergely L Lukacs
doi:10.1038/nchembio.1253



Compounds that restore function to the cystic fibrosis–linked ΔF508 allele of CFTR can be classified on the basis of three corrector functions, representing different targets within the five domains of the channel protein. Combinations of individual compounds in the three classes can restore considerable function to the mutant channel.

Unexpected non-Hoogsteen–based mutagenicity mechanism of FaPy-DNA lesions   pp455 - 461
Tim H Gehrke, Ulrike Lischke, Karola L Gasteiger, Sabine Schneider, Simone Arnold, Heiko C Müller, David S Stephenson, Hendrik Zipse and Thomas Carell
doi:10.1038/nchembio.1254



Certain oxidative DNA lesions adopt altered conformational preferences that lead to mutations during replication. Biochemical and structural data reveal that for formamidopyrimidine lesions, tautomerization and altered base pair geometry in the DNA polymerase active site, rather than changes in glycosidic torsion angle, direct the mutagenicity of these lesions.
Chemical compounds
See also: News and Views by Gates

Allosteric inhibition through suppression of transient conformational states   pp462 - 465
Shiou-Ru Tzeng and Charalampos G Kalodimos
doi:10.1038/nchembio.1250



Advanced NMR studies of catabolite activator protein show that allosteric inhibitors can prevent conformational changes needed for a protein to bind its ligand, offering an explanation for why these inhibitors may not appear to cause any effect when monitored using static techniques.

See also: News and Views by Veglia

Erratum

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Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis   p466
Erik C Hett, Louise H Slater, Kevin G Mark, Tomohiko Kawate, Brian G Monks, Andrea Stutz, Eicke Latz and Deborah T Hung
doi:10.1038/nchembio-0613-466a

Corrigenda

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Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization   p466
Karen Stanger, Micah Steffek, Lijuan Zhou, Christine D Pozniak, Clifford Quan, Yvonne Franke, Jeff Tom, Christine Tam, J Michael Elliott, Joseph W Lewcock, Yingnan Zhang, Jeremy Murray and Rami N Hannoush
doi:10.1038/nchembio-0613-466b

Protein dynamics: Catch them if you can   p466
Gianluigi Veglia
doi:10.1038/nchembio-0613-466c

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