Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

October 10th, 2016 by Gahl Levy

Nature Chemical Biology 12, 1037 (2016). doi:10.1038/nchembio.2193

Authors: Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze, Elishai Ezra, Basak E Uygun, Korkut Uygun, Martin Trippler, Joerg F Schlaak, Oren Shibolet, Ella H Sklan, Merav Cohen, Joerg Timm, Nir Friedman & Yaakov Nahmias

  • Posted in Nat Chem Biol, Publications
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SF2312 is a natural phosphonate inhibitor of enolase

October 10th, 2016 by Paul G Leonard

Nature Chemical Biology 12, 1053 (2016). doi:10.1038/nchembio.2195

Authors: Paul G Leonard, Nikunj Satani, David Maxwell, Yu-Hsi Lin, Naima Hammoudi, Zhenghong Peng, Federica Pisaneschi, Todd M Link, Gilbert R Lee, Duoli Sun, Basvoju A Bhanu Prasad, Maria Emilia Di Francesco, Barbara Czako, John M Asara, Y Alan Wang, William Bornmann, Ronald A DePinho & Florian L Muller

Serine is a new target residue for endogenous ADP-ribosylation on histones

October 10th, 2016 by Orsolya Leidecker

Nature Chemical Biology 12, 998 (2016). doi:10.1038/nchembio.2180

Authors: Orsolya Leidecker, Juan José Bonfiglio, Thomas Colby, Qi Zhang, Ilian Atanassov, Roko Zaja, Luca Palazzo, Anna Stockum, Ivan Ahel & Ivan Matic

ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 unique ADPr sites in human osteosarcoma cells and report serine ADPr as a new type of histone mark that responds to DNA damage.

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Bipartite Role of Hsp90 Keeps CRAF Kinase Poised for Activation [Protein Structure and Folding]

October 5th, 2016 by Mitra, S., Ghosh, B., Gayen, N., Roy, J., Mandal, A. K.

CRAF kinase maintains cell viability, growth and proliferation by participating in MAPK pathway. Unlike BRAF, CRAF requires continuous chaperoning by Hsp90 to retain MAPK signaling. But, the reason behind the continuous association of Hsp90 with CRAF is still elusive. In this study, we have identified the bipartite role of Hsp90 in chaperoning CRAF kinase. Hsp90 facilitates Ser-621 phosphorylation of CRAF and prevents the kinase from degradation. Co-chaperone Cdc37 assists in this phosphorylation event. However, after folding the stability of the kinase becomes insensitive to Hsp90 inhibition, although the physical association between Hsp90 and CRAF remains intact. We observe that over-expression of Hsp90 stimulates MAPK signaling by activating CRAF. The interaction between Hsp90 and CRAF is substantially increased under elevated level of cellular Hsp90 and in presence of either active Ras (RasV12) or EGF. Surprisingly, enhanced binding of Hsp90 to CRAF occurs prior to the Ras-CRAF association and facilitates actin recruitment to CRAF for efficient Ras-CRAF interaction, which is independent of Hsp90s ATPase activity. However, monomeric CRAF (CRAF R401H) shows abrogated interaction with both Hsp90 and actin, thereby affecting Hsp90-dependent CRAF activation. This finding suggests that stringent assemblage of Hsp90 keeps CRAF kinase equipped for participating in MAPK pathway. Thus, the role of Hsp90 in CRAF maturation and activation acts as a limiting factor to maintain the function of a strong client like CRAF kinase.

Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells

October 3rd, 2016 by Cecilia Lopez-Sambrooks

Nature Chemical Biology 12, 1023 (2016). doi:10.1038/nchembio.2194

Authors: Cecilia Lopez-Sambrooks, Shiteshu Shrimal, Carol Khodier, Daniel P Flaherty, Natalie Rinis, Jonathan C Charest, Ningguo Gao, Peng Zhao, Lance Wells, Timothy A Lewis, Mark A Lehrman, Reid Gilmore, Jennifer E Golden & Joseph N Contessa

  • Posted in Nat Chem Biol, Publications
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Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification

October 3rd, 2016 by Zhewang Lin

Nature Chemical Biology 12, 995 (2016). doi:10.1038/nchembio.2190

Authors: Zhewang Lin, Min Dong, Yugang Zhang, Eunyoung Alisa Lee & Hening Lin

Diphthamide and the tRNA wobble uridine modifications both require diphthamide biosynthesis 3 (Dph3) protein as an electron donor for the iron-sulfur clusters in their biosynthetic enzymes. Here, using a proteomic approach, we identified Saccharomyces cerevisiae cytochrome b5 reductase (Cbr1) as a NADH-dependent reductase for Dph3. The NADH- and Cbr1-dependent reduction of Dph3 may provide a regulatory linkage between cellular metabolic state and protein translation.

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Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution

October 3rd, 2016 by Sibel Kalyoncu

Nature Chemical Biology 12, 1031 (2016). doi:10.1038/nchembio.2191

Authors: Sibel Kalyoncu, David P Heaner, Zohre Kurt, Casey M Bethel, Chiamaka U Ukachukwu, Srinivas Chakravarthy, Jim C Spain & Raquel L Lieberman

  • Posted in Nat Chem Biol, Publications
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Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching

October 3rd, 2016 by Chris A Dejong

Nature Chemical Biology 12, 1007 (2016). doi:10.1038/nchembio.2188

Authors: Chris A Dejong, Gregory M Chen, Haoxin Li, Chad W Johnston, Mclean R Edwards, Philip N Rees, Michael A Skinnider, Andrew L H Webster & Nathan A Magarvey

  • Posted in Nat Chem Biol, Publications
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Functional mining of transporters using synthetic selections

October 3rd, 2016 by Hans J Genee

Nature Chemical Biology 12, 1015 (2016). doi:10.1038/nchembio.2189

Authors: Hans J Genee, Anne P Bali, Søren D Petersen, Solvej Siedler, Mads T Bonde, Luisa S Gronenberg, Mette Kristensen, Scott J Harrison & Morten O A Sommer

The AAA+ FtsH Protease Degrades an ssrA-Tagged Model Protein in the Inner Membrane of Escherichia coli

September 30th, 2016 by Sanjay B. Hari and Robert T. Sauer

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b00920