Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis

May 9th, 2016 by Kenichi Shimada

Nature Chemical Biology 12, 497 (2016). doi:10.1038/nchembio.2079

Authors: Kenichi Shimada, Rachid Skouta, Anna Kaplan, Wan Seok Yang, Miki Hayano, Scott J Dixon, Lewis M Brown, Carlos A Valenzuela, Adam J Wolpaw & Brent R Stockwell

  • Posted in Nat Chem Biol, Publications
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The Involvement of His50 during Protein Disulfide Isomerase Binding Is Essential for Inhibiting α-Syn Fibril Formation

May 6th, 2016 by Priyatosh Ranjan and Ashutosh Kumar

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Biochemistry
DOI: 10.1021/acs.biochem.6b00280

Structure and Mechanism of Isopropylmalate Dehydrogenase from Arabidopsis thaliana: Insights on Leucine and Aliphatic Glucosinolate Biosynthesis [Protein Structure and Folding]

May 2nd, 2016 by Lee, S. G., Nwumeh, R., Jez, J. M.

Isopropylmalate dehydrogenase (IPMDH) and 3-(2'-methylthio)ethylmalate dehydrogenase catalyze the oxidative decarboxylation of different beta-hydroxyacids in the leucine and methionine-derived glucosinolate biosynthesis pathways, respectively, in plants. Evolution of the glucosinolate biosynthetic enzyme from IPMDH results from a single amino acid substitution that alters substrate specificity. Here we present the x-ray crystal structures of Arabidopsis thaliana IPMDH2 (AtIPMDH2) in complex with either isopropylmalate and Mg2+ or NAD+. These structures reveal conformational changes that occur upon ligand binding and provide insight on the active site of the enzyme. The x-ray structures and kinetic analysis of site-directed mutants are consistent with a chemical mechanism in which Lys232 activates a water molecule for catalysis. Structural analysis of the AtIPMDH2 K232M mutant and isothermal titration calorimetry supports a key role of Lys232 in the reaction mechanism. This study suggests that IPMDH-like enzymes in both leucine and glucosinolate biosynthesis pathways use a common mechanism and that members of the beta-hydroxyacid reductive decarboxylase family employ different active site features for similar reactions.
  • Posted in Journal of Biological Chemistry, Publications
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Metabolite concentrations, fluxes and free energies imply efficient enzyme usage

May 2nd, 2016 by Junyoung O Park

Nature Chemical Biology 12, 482 (2016). doi:10.1038/nchembio.2077

Authors: Junyoung O Park, Sara A Rubin, Yi-Fan Xu, Daniel Amador-Noguez, Jing Fan, Tomer Shlomi & Joshua D Rabinowitz

  • Posted in Nat Chem Biol, Publications
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An intrinsically disordered entropic switch determines allostery in Phd–Doc regulation

May 2nd, 2016 by Abel Garcia-Pino

Nature Chemical Biology 12, 490 (2016). doi:10.1038/nchembio.2078

Authors: Abel Garcia-Pino, Steven De Gieter, Ariel Talavera, Henri De Greve, Rouslan G Efremov & Remy Loris

  • Posted in Nat Chem Biol, Publications
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Effect of Different Divalent Cations on the Kinetics and Fidelity of RB69 DNA Polymerase

April 28th, 2016 by Ashwani Kumar Vashishtha and William H. Konigsberg

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Biochemistry
DOI: 10.1021/acs.biochem.5b01350

A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate

April 25th, 2016 by Michael E Pacold

Nature Chemical Biology 12, 452 (2016). doi:10.1038/nchembio.2070

Authors: Michael E Pacold, Kyle R Brimacombe, Sze Ham Chan, Jason M Rohde, Caroline A Lewis, Lotteke J Y M Swier, Richard Possemato, Walter W Chen, Lucas B Sullivan, Brian P Fiske, Steve Cho, Elizaveta Freinkman, Kıvanç Birsoy, Monther Abu-Remaileh, Yoav D Shaul, Chieh Min Liu, Minerva Zhou, Min Jung Koh, Haeyoon Chung, Shawn M Davidson, Alba Luengo, Amy Q Wang, Xin Xu, Adam Yasgar, Li Liu, Ganesha Rai, Kenneth D Westover, Matthew G Vander Heiden, Min Shen, Nathanael S Gray, Matthew B Boxer & David M Sabatini

  • Posted in Nat Chem Biol, Publications
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A small molecule mitigates hearing loss in a mouse model of Usher syndrome III

April 25th, 2016 by Kumar N Alagramam

Nature Chemical Biology 12, 444 (2016). doi:10.1038/nchembio.2069

Authors: Kumar N Alagramam, Suhasini R Gopal, Ruishuang Geng, Daniel H-C Chen, Ina Nemet, Richard Lee, Guilian Tian, Masaru Miyagi, Karine F Malagu, Christopher J Lock, William R K Esmieu, Andrew P Owens, Nicola A Lindsay, Krista Ouwehand, Faywell Albertus, David F Fischer, Roland W Bürli, Angus M MacLeod, William E Harte, Krzysztof Palczewski & Yoshikazu Imanishi

  • Posted in Nat Chem Biol, Publications
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Click-EM for imaging metabolically tagged nonprotein biomolecules

April 25th, 2016 by John T Ngo

Nature Chemical Biology 12, 459 (2016). doi:10.1038/nchembio.2076

Authors: John T Ngo, Stephen R Adams, Thomas J Deerinck, Daniela Boassa, Frances Rodriguez-Rivera, Sakina F Palida, Carolyn R Bertozzi, Mark H Ellisman & Roger Y Tsien

Protein synthesis: Taming transmembrane proteins

April 19th, 2016 by Caitlin Deane

Nature Chemical Biology 12, 305 (2016). doi:10.1038/nchembio.2073

Author: Caitlin Deane