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Nature Chemical Biology Contents: March 2016, Volume 12 No 3 pp 125 - 199

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TABLE OF CONTENTS

March 2016 Volume 12, Issue 3

Research Highlights
News and Views
Perspective
Brief Communication
Articles

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Research Highlights

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Optogenetics: Follow the PIF | Target identification: Getting cholesterol out | Catalytic DNA: Ligating with lambda | RNA modification: Translating for growth


News and Views

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RNA conformation: Lightening up invisible states   pp126 - 127
Yun-Xing Wang
doi:10.1038/nchembio.2030
The versatility of RNA is achieved in part through its ability to adopt various shapes of structures. A new technology called X-ray scattering interferometry enables the detection of 'invisible' states by lighting up gold pairs tagged to RNA molecules.

See also: Article by Shi et al.

Translation: Ribosomes make sweeping arrests   pp127 - 128
Diego A Alonzo and T Martin Schmeing
doi:10.1038/nchembio.2027
The arrest peptides that function with the macrolide antibiotic erythromycin stall translating ribosomes in the presence of the antibiotic, leading to remodeling of the downstream mRNA and enhancement of the translation of resistance genes. Current work suggests that small changes in the nascent peptide dictate the ability of ribosomes to respond to this and other small molecules.

See also: Article by Gupta et al.

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Perspective

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Development and application of bond cleavage reactions in bioorthogonal chemistry   pp129 - 137
Jie Li and Peng R Chen
doi:10.1038/nchembio.2024



Bioorthogonal chemistry approaches have traditionally focused on selective ligation reactions between compatible reactive groups. This Perspective highlights progress in developing bioorthogonal cleavage reactions for diverse applications in chemical biology.

Brief Communication

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Addicting diverse bacteria to a noncanonical amino acid   pp138 - 140
Drew S Tack, Jared W Ellefson, Ross Thyer, Bo Wang, Jimmy Gollihar et al.
doi:10.1038/nchembio.2002



Expansion of the genetic code to noncanonical amino acids (NCAAs) has been limited by the lack of evolutionary pressure for organismal dependence on the NCAA. Linking bacterial survival to an engineered β-lactamase that requires a non-natural tyrosine analog engenders diverse bacteria with a stable, expanded genetic code.

Articles

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Protonation of a glutamate residue modulates the dynamics of the drug transporter EmrE   pp141 - 145
Anindita Gayen, Maureen Leninger and Nathaniel J Traaseth
doi:10.1038/nchembio.1999



The protonation state of Glu14 within the drug transporter EmrE is able to influence the conformational dynamics of the protein and thereby bias the inward-open conformation to facilitate substrate efflux.

The solution structural ensembles of RNA kink-turn motifs and their protein complexes   pp146 - 152
Xuesong Shi, Lin Huang, David M J Lilley, Pehr B Harbury and Daniel Herschlag
doi:10.1038/nchembio.1997



XSI analysis of two RNA kink-turn motifs, KtA and KtB, in a range of solution concentrations and in the presence of the kink-turn protein partner L7Ae reveals a restricted conformational ensemble that is regulated by ions and protein binding.

See also: News and Views by Wang

Nascent peptide assists the ribosome in recognizing chemically distinct small molecules   pp153 - 158
Pulkit Gupta, Bo Liu, Dorota Klepacki, Vrinda Gupta, Klaus Schulten et al.
doi:10.1038/nchembio.1998



Point mutations in nascent peptides that regulate in the macrolide antibiotic resistance genes ermC and ermB can tune the recognition of the antibiotics erythromycin and telithromycin that control ribosome stalling and gene activation.

See also: News and Views by Alonzo & Schmeing

Frequency and amplitude control of cortical oscillations by phosphoinositide waves   pp159 - 166
Ding Xiong, Shengping Xiao, Su Guo, Qingsong Lin, Fubito Nakatsu et al.
doi:10.1038/nchembio.2000



Oscillations of actin, FBP17 and N-WASP are coupled to phase-shifted phosphoinositide (PI) turnover that is regulated by the lipid phosphatases SHIP1, synaptojanin 2 and PI 3-kinases. PI(4,5)P2 turnover regulates wave amplitude and PI(3,4)P2 acts as a pacemaker.

A topological and conformational stability alphabet for multipass membrane proteins   pp167 - 173
Xiang Feng and Patrick Barth
doi:10.1038/nchembio.2001



A scan of the protein structure database looking for interhelical contacts across transmembrane protein helix trimers finds six distinct structural and topological classes with unique sequence-3D contact motifs that could prove useful in future protein design initiatives.

Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence   pp174 - 179
Feifei Chen, Hongxia Di, Youxin Wang, Qiao Cao, Bin Xu et al.
doi:10.1038/nchembio.2003



The antifungal drug naftifine blocks carotenoid pigment biosynthesis in Staphylococcus aureus through inhibition of a biosynthetic enzyme of staphyloxanthin, disabling an important virulence mechanism and thus making the pathogen susceptible to host oxidant killing.
Chemical compounds

A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1   pp180 - 187
Jacob I Stuckey, Bradley M Dickson, Nancy Cheng, Yanli Liu, Jacqueline L Norris et al.
doi:10.1038/nchembio.2007



Chromodomains in chromatin-associated proteins act as 'readers' of methylated lysines within histones. Structural and computational design led to the identification of UNC3866, a potent, cell-active peptide-based inhibitor of the methyllysine reading functions of CBX and CDY chromodomains.
Chemical compounds

A two-state activation mechanism controls the histone methyltransferase Suv39h1   pp188 - 193
Manuel M Muller, Beat Fierz, Lenka Bittova, Glen Liszczak and Tom W Muir
doi:10.1038/nchembio.2008



Suv39h1 is a histone methyltransferase that methylates H3K9 residues in heterochromatic regions of the genome. An approach using semisynthetic chromatin reveals a mechanism for heterochromatin spreading in which H3K9 trimethylation anchors and activates Suv39h1 for modification of proximal lysines.

A pyridoxal phosphate-dependent enzyme that oxidizes an unactivated carbon-carbon bond   pp194 - 199
Yi-Ling Du, Rahul Singh, Lona M Alkhalaf, Eugene Kuatsjah, Hai-Yan He et al.
doi:10.1038/nchembio.2009



Pyridoxal 5-phosphate (PLP) is an essential coenzyme involved in diverse amino acid transformations. The discovery that Ind4 catalyzes the PLP-dependent oxidation of an unactivated carbon of L-arginine, as a part of the indolmycin biosynthetic pathway, expands the scope of reactions facilitated by PLP-dependent enzymes.

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