Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain

September 5th, 2016 by Gizem Akçay

Nature Chemical Biology 12, 931 (2016). doi:10.1038/nchembio.2174

Authors: Gizem Akçay, Matthew A Belmonte, Brian Aquila, Claudio Chuaqui, Alexander W Hird, Michelle L Lamb, Philip B Rawlins, Nancy Su, Sharon Tentarelli, Neil P Grimster & Qibin Su

  • Posted in Nat Chem Biol, Publications
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Simultaneous analysis of enzyme structure and activity by kinetic capillary electrophoresis–MS

September 5th, 2016 by Gleb G Mironov

Nature Chemical Biology 12, 918 (2016). doi:10.1038/nchembio.2170

Authors: Gleb G Mironov, Christopher M Clouthier, Abdullah Akbar, Jeffrey W Keillor & Maxim V Berezovski

  • Posted in Nat Chem Biol, Publications
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YidC assists the stepwise and stochastic folding of membrane proteins

September 5th, 2016 by Tetiana Serdiuk

Nature Chemical Biology 12, 911 (2016). doi:10.1038/nchembio.2169

Authors: Tetiana Serdiuk, Dhandayuthapani Balasubramaniam, Junichi Sugihara, Stefania A Mari, H Ronald Kaback & Daniel J Müller

  • Posted in Nat Chem Biol, Publications
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Summer 2016 newsletter released

August 31st, 2016 by pthomas2

Welcome back from the ACS meeting in Philadelphia! The summer newsletter was just released. BIOL members should have received it in their email. You can find the newsletter here.

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

August 29th, 2016 by Tinghu Zhang

Nature Chemical Biology 12, 876 (2016). doi:10.1038/nchembio.2166

Authors: Tinghu Zhang, Nicholas Kwiatkowski, Calla M Olson, Sarah E Dixon-Clarke, Brian J Abraham, Ann K Greifenberg, Scott B Ficarro, Jonathan M Elkins, Yanke Liang, Nancy M Hannett, Theresa Manz, Mingfeng Hao, Bartlomiej Bartkowiak, Arno L Greenleaf, Jarrod A Marto, Matthias Geyer, Alex N Bullock, Richard A Young & Nathanael S Gray

  • Posted in Nat Chem Biol, Publications
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Dual action antifungal small molecule modulates multidrug efflux and TOR signaling

August 29th, 2016 by Tanvi Shekhar-Guturja

Nature Chemical Biology 12, 867 (2016). doi:10.1038/nchembio.2165

Authors: Tanvi Shekhar-Guturja, G M Kamal B Gunaherath, E M Kithsiri Wijeratne, Jean-Philippe Lambert, Anna F Averette, Soo Chan Lee, Taeyup Kim, Yong-Sun Bahn, Farida Tripodi, Ron Ammar, Katja Döhl, Karolina Niewola-Staszkowska, Lutz Schmitt, Robbie J Loewith, Frederick P Roth, Dominique Sanglard, David Andes, Corey Nislow, Paola Coccetti, Anne-Claude Gingras, Joseph Heitman, A A Leslie Gunatilaka & Leah E Cowen

  • Posted in Nat Chem Biol, Publications
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Genetic code expansion in the mouse brain

August 29th, 2016 by Russell J Ernst

Nature Chemical Biology 12, 776 (2016). doi:10.1038/nchembio.2160

Authors: Russell J Ernst, Toke P Krogager, Elizabeth S Maywood, Roberto Zanchi, Václav Beránek, Thomas S Elliott, Nicholas P Barry, Michael H Hastings & Jason W Chin

Site-specific incorporation of non-natural amino acids into proteins, via genetic code expansion with pyrrolysyl tRNA synthetase (PylRS) and tRNAPylCUA pairs (and their evolved derivatives) from Methanosarcina sp., forms the basis of powerful approaches to probe and control protein function in cells and invertebrate organisms. Here we demonstrate that adeno-associated viral delivery of these pairs enables efficient genetic code expansion in primary neuronal culture, organotypic brain slices and the brains of live mice.

Proof of Principle: Coronin 1A – An Intrinsic Modulator of T Lymphocyte Function [Signal Transduction]

August 26th, 2016 by Siegmund, K., Klepsch, V., Hermann-Kleiter, N., Baier, G.

Coronins are evolutionarily conserved proteins that were originally identified as modulators of actin-dependent processes. Studies analyzing complete Coronin 1a knockout mice have shown that this molecule is an important regulator of T cell homeostasis and it has been linked to immune deficiencies as well as autoimmune disorders. Nevertheless, since Coronin 1A is strongly expressed in all leukocyte subsets, it is not conclusive whether or not this phenotype is attributed to a T cell-intrinsic function of Coronin 1A. To address this research question, we have generated a T cell-specific Coronin 1a knockout mouse (Coro1afl/fl x Cd4[Cre]). Deletion of Coro1a specifically in T cells led to a strong reduction in T cell number and a shift towards the effector/memory phenotype in peripheral lymphoid organs when compared to Cd4[Cre] mice expressing wild-type Coro1a. In contrast to peripheral lymphoid tissue, thymocyte number and subsets were not affected by the deletion of Coro1a. Furthermore, T cell-specific Coro1a knockout mice were largely resistant to the induction of autoimmunity when tested in the MOG-induced EAE mouse model of multiple sclerosis. Thus, the phenotype of T cell-specific Coro1a deletion resembles the phenotype observed with conventional (whole body) Coro1a knockout mice. In summary, our findings provide formal proof of the predominant T cell-intrinsic role of Coronin 1A.

Leptin Enhances TH2 and ILC2 Responses in Allergic Airway Disease [Molecular Bases of Disease]

August 26th, 2016 by Zheng, H., Zhang, X., Castillo, E. F., Luo, Y., Liu, M., Yang, X. O.

Allergic asthma and obesity are the leading health problems in the world. Many studies have shown that obesity is a risk factor of development of asthma. However, the underlying mechanism has not been well established. In this study, we demonstrate that leptin, an adipokine elevated in obese individuals, promoted proliferation and survival of pro-allergic type 2 helper T cells and group 2 innate lymphoid cells and production of type 2 cytokines, which together contribute to allergic responses. Leptin activates mTORC1, MAPK and STAT3 pathways in TH2 cells. The effects of leptin on TH2 cell proliferation, survival and cytokine production are dependent on the mTORC1 and MAPK pathways as revealed by specific inhibitors. In vivo, leptin-deficiency led to attenuated experimental allergic airway inflammation. Our results thus support that obesity associated elevation of leptin may increase the susceptibility of asthma via modulation of pro-allergic lymphocyte responses.

Nuclear Magnetic Resonance Observation of α-Synuclein Membrane Interaction by Monitoring the Acetylation Reactivity of Its Lysine Side Chains

August 23rd, 2016 by Jung Ho Lee, Jinfa Ying and Ad Bax

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b00637