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vrijdag 18 augustus 2017

Nature Chemical Biology Contents: September 2017, Volume 13 No 9 pp 923 - 1052

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Nature Chemical Biology

Nature Reviews Chemistry is an online-only journal that provides both an introduction to chemists embarking on a new topic of investigation and thought-provoking, in-depth sections for the expert. The journal also publishes regular columns which focus on the teaching of chemistry and on the translation of research into business opportunities.


September 2017 Volume 13, Issue 9

Research Highlights
News and Views

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Nature Catalysis is a new online-only journal that will publish work on all areas of catalysis. The journal will provide coverage of the science and business of catalysis research, creating a unique journal for scientists, engineers, and researchers in industry. Nature Catalysis is launching in January 2018 and is now open for submissions. 


Research Highlights


Ubiquitin-proteasome system: Rescuing EBV latency | Protein design: I like to fold it, fold it | Bacterial immunity: A virtuous CRISPR cycle | Neurobiology: Lighting up neurons

News and Views


Extracellular vesicles: Taking metabolism on the road   pp924 - 925
Lucas B Sullivan
Extracellular vesicles (EVs) are a class of secreted membrane particles capable of transferring biological molecules between cells. Metabolomics measurements indicate that isolated EVs also have autonomous metabolic enzyme activities, including the unexpected identification of endogenous human asparaginase activity.

See also: Article by Iraci et al.

Drug development: Locking down metabolism   pp925 - 926
William R Bishai
An allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase—an enzyme that is nonessential for in vitro growth—has potent antimicrobial activity, revealing a potentially expanded target list for antimicrobials and greater chemical space for new inhibitors.

See also: Article by Wellington et al.

Protein engineering: Redirecting membrane machinery   pp927 - 928
Kalistyn Burley and Celia W Goulding
The ability to solubilize membrane proteins while retaining their native function is a persistent challenge. Re-engineering of the membrane protein DsbB into a soluble cytoplasmic version maintained its activity and enabled recompartmentalization of the periplasmic DsbAB disulfide bond-forming system.

See also: Article by Mizrachi et al.

Nature Chemical Biology
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A kinetic view of GPCR allostery and biased agonism   pp929 - 937
J Robert Lane, Lauren T May, Robert G Parton, Patrick M Sexton and Arthur Christopoulos

Allosteric modulation and biased agonism at GPCRs could be manifestations of the same underlying 'conformational selection' mechanism, and these can be harmonized by considering the influence of ligand-receptor residence time and kinetic context.



A molecular rheostat maintains ATP levels to drive a synthetic biochemistry system   pp938 - 942
Paul H Opgenorth, Tyler P Korman, Liviu Iancu and James U Bowie

An enzymatic rheostat controls ATP levels by regulating flux through two pathways depending on free phosphate levels. Incorporation of this rheostat overcomes ATPase contamination and improves isobutanol production from glucose in a cell-free system.

A small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase   pp943 - 950
Samantha Wellington, Partha P Nag, Karolina Michalska, Stephen E Johnston, Robert P Jedrzejczak et al.

High-throughput screening identifies an inhibitor of the interaction between α- and β-subunits of the Mycobacterium tuberculosis (Mtb) tryptophan synthase, TrpAB, that allows for defining TrpAB as essential for Mtb infection, independent of a T cell response.
Chemical compounds
See also: News and Views by Bishai

Extracellular vesicles are independent metabolic units with asparaginase activity   pp951 - 955
Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S H Costa, Chiara Cossetti et al.

Metabolomics analysis of neural stem/progenitor cell-derived extracellular vesicles reveals asparaginase activity catalyzed by L-asparaginase-like protein 1.

See also: News and Views by Sullivan

The structure of vanadium nitrogenase reveals an unusual bridging ligand   pp956 - 960
Daniel Sippel and Oliver Einsle

The structure of vanadium nitrogenase reveals key differences from its counterpart molybdenum nitrogenase, particularly in the way it ligands its FeV cofactor, that help to explain the basis for the unique properties of these two nitrogenases.

Allosteric sensitization of proapoptotic BAX   pp961 - 967
Jonathan R Pritz, Franziska Wachter, Susan Lee, James Luccarelli, Thomas E Wales et al.

An NMR fragment screen identified a small molecule that binds to an allosteric site on the proapoptotic protein BAX and synergizes with the BIM BH3 domain to conformationally activate BAX and enhance BAX-mediated membrane poration.
Chemical compounds

An excited state underlies gene regulation of a transcriptional riboswitch   pp968 - 974
Bo Zhao, Sharon L Guffy, Benfeard Williams and Qi Zhang

The use of chemical exchange saturation transfer NMR reveals a previously hidden excited conformational state of the fluoride riboswitch, providing a model in which ligand binding allosterically suppresses a linchpin base pair to activate transcription.

Structures of carboxylic acid reductase reveal domain dynamics underlying catalysis   pp975 - 981
Deepankar Gahloth, Mark S Dunstan, Daniela Quaglia, Evaldas Klumbys, Michael P Lockhart-Cairns et al.

Structural characterization of carboxylic acid reductase in multiple didomain configurations, coupled with mutagenesis, reveals how the enzyme transitions into a catalytically competent orientation and prevents over-reduction of its aldehyde product.

Functional annotation of chemical libraries across diverse biological processes   pp982 - 993
Jeff S Piotrowski, Sheena C Li, Raamesh Deshpande, Scott W Simpkins, Justin Nelson et al.

Profiling of over 13,000 compounds against yeast gene deletion mutants, defining the differential responses on cells, reveals chemical-genetic interactions that can be used to predict compound function and their target pathways.

Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration   pp994 - 1001
Haiming Jiang, Rong Deng, Xiuyan Yang, Jialin Shang, Shaoyong Lu et al.

Adenomatous polyposis coli (APC) is shown to promote colorectal cancer cell migration by activating the guanine nucleotide exchange factor Asef. Structure-based design resulted in the development of peptidomimetic inhibitors that disrupted APC-Asef interactions.

Toxicity and repair of DNA adducts produced by the natural product yatakemycin   pp1002 - 1008
Elwood A Mullins, Rongxin Shi and Brandt F Eichman

Biophysical and structural analyses reveal how the glycosylase AlkD utilizes a mechanism of excision that does not involve base flipping to enable an alternative repair pathway for large yatakemycin-DNA adducts.

FRET monitoring of a nonribosomal peptide synthetase   pp1009 - 1015
Jonas Alfermann, Xun Sun, Florian Mayerthaler, Thomas E Morrell, Eva Dehling et al.

FRET sensors based on the adenylation and peptidyl carrier protein domains of a nonribosomal peptide synthetase illuminate the relationships between conformational dynamics and the catalytic cycle of this multidomain assembly line enzyme.

Copper import in Escherichia coli by the yersiniabactin metallophore system   pp1016 - 1021
Eun-Ik Koh, Anne E Robinson, Nilantha Bandara, Buck E Rogers and Jeffrey P Henderson

Under high-copper conditions, yersiniabactin (Ybt) binds copper (Cu) to prevent toxicity. Ybt is now shown to mediate Cu import under low-Cu conditions through formation of a Cu(II)-Ybt complex resulting in metalation of a Cu-requiring enzyme.

A water-soluble DsbB variant that catalyzes disulfide-bond formation in vivo   pp1022 - 1028
Dario Mizrachi, Michael-Paul Robinson, Guoping Ren, Na Ke, Mehmet Berkmen et al.

The design of a water-soluble variant of the integral membrane protein DsbB and its coexpression with an export-defective copy of DsbA facilitates disulfide-bond formation in the Escherichia coli cytoplasm in a quinone-dependent fashion.

See also: News and Views by Burley & Goulding

Molecular basis of the evolution of alternative tyrosine biosynthetic routes in plants   pp1029 - 1035
Craig A Schenck, Cynthia K Holland, Matthew R Schneider, Yusen Men, Soon Goo Lee et al.

Structural, biochemical, and phylogenetic analyses of plant prephenate and arogenate dehydrogenases reveal a single residue that defines substrate specificity and sensitivity to product inhibition in two divergent tyrosine biosynthetic pathways.

2′-Deoxyadenosine 5′-diphosphoribose is an endogenous TRPM2 superagonist   pp1036 - 1044
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Perez, Joanna M Watt, Monika D Rozewitz et al.

2′-Deoxy-ADPR, formed from the combined action of NMNAT and CD38 in response to H2O2 signaling, activates TRPM2 ion channel currents more potently than the known agonist ADPR via a deceleration of channel inactivation and a higher average open probability.
Chemical compounds

Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor   pp1045 - 1052
Yichong Fan, Merna Makar, Michael X Wang and Hui-wang Ai

A fluorescent biosensor to monitor thioredoxin (Trx) redox activity called TrxRFP1 was developed by genetically linking Trx1 to the redox-sensitive red fluorescent protein rxRFP1. TrxRFP1 was used to detect redox dynamics induced by various chemicals, serum, or epidermal growth factor.

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