Thursday, August 18, 2016

Nature Chemical Biology Contents: September 2016, Volume 12 No 9 pp 657 - 762

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TABLE OF CONTENTS

September 2016 Volume 12, Issue 9

Research Highlights
News and Views
Perspective
Brief Communication
Articles

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Research Highlights

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Plant biology: Shoot for the top | Innate immunity: A sweet switch | Chemical synthesis: Linking up lysines | Gut microbiome: Branching into metabolic disease


News and Views

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Small-Molecule inhibitors: Weed-control measures   pp658 - 659
Koichi Yoneyama
doi:10.1038/nchembio.2155
A high-throughput screen in the model plant Arabidopsis unveils leads for potential agents to combat Striga, a devastating root parasitic weed that affects food crops in Sub-Saharan Africa.

See also: Article by Holbrook-Smith et al.

Target validation: Switching domains   pp659 - 660
Alessio Ciulli
doi:10.1038/nchembio.2154
Chemical probes and drugs often bind to functional domains on disease-relevant proteins. A study suggests a chemical genetic approach to establish on-target effects by swapping the targeted domain, affording resistance to pharmacological inhibition while retaining functionality.

See also: Article by Hohmann et al.

Structural biology: HDAC6 finally crystal clear   pp660 - 661
Yanli Liu, Li Li and Jinrong Min
doi:10.1038/nchembio.2158
Crystal structures of both catalytic domains of HDAC6 provide insights into the mechanisms of deacetylation for their specific substrates and a structural basis for understanding selective inhibition of HDAC6.

See also: Article by Hai & Christianson | Article by Miyake et al.

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Perspective

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Insights into newly discovered marks and readers of epigenetic information   pp662 - 668
Forest H Andrews, Brian D Strahl and Tatiana G Kutateladze
doi:10.1038/nchembio.2149



A Perspective focused on post-translational modifications of histone proteins and their selective recognition by epigenetic 'readers' highlights the importance of structural insights in understanding these key interactions in gene expression regulation.

Brief Communication

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A calcium-dependent acyltransferase that produces N-acyl phosphatidylethanolamines   pp669 - 671
Yuji Ogura, William H Parsons, Siddhesh S Kamat and Benjamin F Cravatt
doi:10.1038/nchembio.2127



An activity-based proteomic strategy identifies PLA2G4E as the calcium-dependent N-acyltransferase that generates an unusual triacylated class of lipids, the NAPEs, which are precursors to bioactive lipids including the endogenous cannabinoid anandamide.

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Articles

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Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition   pp672 - 679
Anja F Hohmann, Laetitia J Martin, Jessica L Minder, Jae-Seok Roe, Junwei Shi et al.
doi:10.1038/nchembio.2115



Acute myeloid leukemia (AML) cells require BRD9 to regulate MYC gene expression and prevent myeloid differentiation. Selective inhibition of BRD9 using a chemical probe that was validated using a resistant bromodomain-swap allele of BRD9 limits AML cell growth.
Chemical compounds
See also: News and Views by Ciulli

A reactivity-based probe of the intracellular labile ferrous iron pool   pp680 - 685
Benjamin Spangler, Charles W Morgan, Shaun D Fontaine, Mark N Vander Wal, Christopher J Chang et al.
doi:10.1038/nchembio.2116



A reactivity-based probe containing an iron-sensitive 1,2,4-trixolane ring conjugated to a small molecule payload combined with a high-throughput immunofluorescence assay enables the selective detection of labile intracellular ferrous iron.
Chemical compounds

ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity   pp686 - 693
Baoen Chen, Baohui Zheng, Michael DeRan, Gopala K Jarugumilli, Jianjun Fu et al.
doi:10.1038/nchembio.2119



The use of activity-based chemical probes revealed that Scribble is palmitoylated at cysteine residues by the palmitoyl acyltransferase ZDHHC7. Loss of Scribble palmitoylation results in loss of cell polarity and its tumor suppressor activity.
Chemical compounds

Tbx16 regulates hox gene activation in mesodermal progenitor cells   pp694 - 701
Alexander Y Payumo, Lindsey E McQuade, Whitney J Walker, Sayumi Yamazoe and James K Chen
doi:10.1038/nchembio.2124



Photoactivable caged morpholinos combined with whole-transcriptome sequencing revealed Tbx16-mediated suppression of posterior hox genes in zebrafish mesodermal progenitor cells.

Pistol ribozyme adopts a pseudoknot fold facilitating site-specific in-line cleavage   pp702 - 708
Aiming Ren, Nikola Vusurovic, Jennifer Gebetsberger, Pu Gao, Michael Juen et al.
doi:10.1038/nchembio.2125



Structural and biochemical analysis of the recently discovered env25 pistol ribozyme reveal an active site containing a pseudoknot that enforces in-line nucleophilic attack at the scissile phosphate and positions nucleotides for general acid and general base catalysis.

Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor   pp709 - 716
Alem W Kahsai, James W Wisler, Jungmin Lee, Seungkirl Ahn, Thomas J Cahill III et al.
doi:10.1038/nchembio.2126



Evolution of RNA aptamers that act allosterically by recognizing and stabilizing specific conformations, including active, inactive, and ligand-specific conformations of the GPCR β2-adrenergic receptor, bound to pharmacologically distinct ligands.

Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins   pp717 - 723
Yu Chen, Fan Yang, Lorena Zubovic, Tom Pavelitz, Wen Yang et al.
doi:10.1038/nchembio.2128



Rational design of the RNA recognition motif (RRM) of Rbfox promotes sequence-specific interaction with the terminal loop of miR-21 precursor. Replacement of the Dicer PAZ domain with this engineered Rbfox RRM enables specific degradation of pre-miR-21.

Small-molecule antagonists of germination of the parasitic plant Striga hermonthica   pp724 - 729
Duncan Holbrook-Smith, Shigeo Toh, Yuichiro Tsuchiya and Peter McCourt
doi:10.1038/nchembio.2129



A small-molecule screen examining the inhibition of Arabidopsis hypocotyl growth and seed germination identified an antagonist of strigolactone signaling, soporidine, that interacted with the strigolactone receptor AtHTL and blocked Striga germination.
Chemical compounds
See also: News and Views by Yoneyama

Structure and function of the bacterial decapping enzyme NudC   pp730 - 734
Katharina Hofer, Sisi Li, Florian Abele, Jens Frindert, Jasmin Schlotthauer et al.
doi:10.1038/nchembio.2132



Structural and biochemical studies of the bacterial NAD-decapping enzyme, NudC, in complex with NAD or its cleavage product NMN reveal the critical residues for substrate recognition and the preference of NudC for NAD-capped RNA.

Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations   pp735 - 740
Hongjun Yu, Hideyuki Takeuchi, Megumi Takeuchi, Qun Liu, Joshua Kantharia et al.
doi:10.1038/nchembio.2135



Structural and biochemical studies of the Notch O-glucosyltransferase Rumi in complex with its substrates inform on the catalytic mechanism for Rumi substrate recognition, and characterization of cancer mutations in Rumi reveals loss of enzyme activity.

Histone deacetylase 6 structure and molecular basis of catalysis and inhibition   pp741 - 747
Yang Hai and David W Christianson
doi:10.1038/nchembio.2134



Histone deacetylase 6 (HDAC6) is a cytoplasmic HDAC that is unusual in having two adjacent catalytic domains. Kinetic data and X-ray crystallographic analyses of human and zebrafish HDAC6 enzymes provide insight into HDAC6 catalysis and its inhibition by small molecules.
Chemical compounds
See also: News and Views by Liu et al.

Structural insights into HDAC6 tubulin deacetylation and its selective inhibition   pp748 - 754
Yasuyuki Miyake, Jeremy J Keusch, Longlong Wang, Makoto Saito, Daniel Hess et al.
doi:10.1038/nchembio.2140



X-ray crystallographic analysis reveals features of the tandem catalytic domains of histone deacetylase 6 (HDAC6), their inhibition by small molecules and functional insights into the enzyme's role in tubulin deacetylation.

See also: News and Views by Liu et al.

Photoswitchable diacylglycerols enable optical control of protein kinase C   pp755 - 762
James Allen Frank, Dmytro A Yushchenko, David J Hodson, Noa Lipstein, Jatin Nagpal et al.
doi:10.1038/nchembio.2141



A photoswitchable diacylglycerol enables spatiotemporal control of membrane translocation of C1-domain-containing proteins and protein kinase C activation to modulate calcium oscillations and vesicle release for synaptic transmission.
Chemical compounds

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