Glycomics: Highlights for carbohydrates

July 19th, 2016 by Terry L. Sheppard

Nature Chemical Biology 12, 575 (2016). doi:10.1038/nchembio.2136

Author: Terry L. Sheppard

Antibiotics: I want a new drug

July 19th, 2016 by Joshua M. Finkelstein

Nature Chemical Biology 12, 575 (2016). doi:10.1038/nchembio.2137

Author: Joshua M. Finkelstein

Chaperones: Speedy motion for function

July 19th, 2016 by Hagen Hofmann

Nature Chemical Biology 12, 576 (2016). doi:10.1038/nchembio.2130

Author: Hagen Hofmann

Hsp90 is an energy-consuming molecular chaperone that activates oncogenic proteins in a complicated multi-step reaction. Photoinduced electron transfer (PET) quenching experiments with a fluorescent reporter have now identified molecular transitions at multiple timescales in the chaperone cycle of Hsp90.

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

July 19th, 2016 by Michael E Pacold

Nature Chemical Biology 12, 656 (2016). doi:10.1038/nchembio0816-656

Author: 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-Remaileh Abu, 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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An oral load of [13C3]glycerol and blood NMR analysis detect fatty acid esterification, pentose phosphate pathway and glycerol metabolism through the tricarboxylic acid cycle in human liver [Lipids]

July 18th, 2016 by Jin, E. S., Sherry, A. D., Malloy, C. R.

Drugs and other interventions for high-impact hepatic diseases often target biochemical pathways such as gluconeogenesis, lipogenesis or the metabolic response to oxidative stress. However, traditional liver function tests do not provide quantitative data about these pathways. In this study, we developed a simple method to evaluate these processes by NMR analysis of plasma metabolites. Healthy subjects ingested [U-13C3]glycerol and blood was dawn at multiple times. Each subject completed three visits under differing nutritional states. High resolution 13C NMR spectra of plasma triacylglycerols and glucose provided new insights into a number of hepatic processes including fatty acid esterification, the pentose phosphate pathway, and gluconeogenesis through the tricarboxylic acid cycle. Fasting stimulated pentose phosphate pathway activity and metabolism of [U-13C3]glycerol in the tricarboxylic acid cycle prior to gluconeogenesis or glyceroneogenesis. Fatty acid esterification was transient in the fasted state, but continuous under fed conditions. We conclude that a simple NMR analysis of blood metabolites provides an important biomarker of pentose phosphate pathway activity, triacylglycerol synthesis and flux through anaplerotic pathways in mitochondria of human liver.
  • Posted in Journal of Biological Chemistry, Publications
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Small-molecule antagonists of germination of the parasitic plant Striga hermonthica

July 18th, 2016 by Duncan Holbrook-Smith

Nature Chemical Biology 12, 724 (2016). doi:10.1038/nchembio.2129

Authors: Duncan Holbrook-Smith, Shigeo Toh, Yuichiro Tsuchiya & Peter McCourt

  • Posted in Nat Chem Biol, Publications
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Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins

July 18th, 2016 by Yu Chen

Nature Chemical Biology 12, 717 (2016). doi:10.1038/nchembio.2128

Authors: Yu Chen, Fan Yang, Lorena Zubovic, Tom Pavelitz, Wen Yang, Katherine Godin, Matthew Walker, Suxin Zheng, Paolo Macchi & Gabriele Varani

  • Posted in Nat Chem Biol, Publications
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Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations

July 18th, 2016 by Hongjun Yu

Nature Chemical Biology 12, 735 (2016). doi:10.1038/nchembio.2135

Authors: Hongjun Yu, Hideyuki Takeuchi, Megumi Takeuchi, Qun Liu, Joshua Kantharia, Robert S Haltiwanger & Huilin Li

  • Posted in Nat Chem Biol, Publications
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Structure and function of the bacterial decapping enzyme NudC

July 18th, 2016 by Katharina Höfer

Nature Chemical Biology 12, 730 (2016). doi:10.1038/nchembio.2132

Authors: Katharina Höfer, Sisi Li, Florian Abele, Jens Frindert, Jasmin Schlotthauer, Julia Grawenhoff, Jiamu Du, Dinshaw J Patel & Andres Jäschke

High affinity binding of the receptor-associated protein D1D2 domains with the LDL receptor-related protein (LRP1) involves bivalent complex formation: Critical roles of lysine 60 and 191. [Molecular Biophysics]

July 11th, 2016 by Prasad, J. M., Young, P. A., Strickland, D. K.

The LDL receptor-related protein 1 (LRP1) is a large endocytic receptor that binds and mediates the endocytosis of numerous structurally diverse ligands. Currently, the basis for ligand recognition by LRP1 is not well understood. LRP1 requires a molecular chaperone, termed the receptor-associated protein (RAP), to escort the newly synthesized receptor from the endoplasmic reticulum to the Golgi. RAP is a three domain protein that contains two high affinity binding sites for LRP1: one located within domains 1 and 2, and one located in its third domain. Studies on the interaction of the RAP third domain with LRP1 reveal critical contributions by lysine 256 and lysine 270 for this interaction. From these studies, a model for ligand recognition by this class of receptors has been proposed. Here we employed surface plasmon resonance to investigate the binding of RAP D1D2 to LRP1. Our results reveal that the high affinity of D1D2 for LRP1 results from avidity effects mediated by the simultaneous interactions of lysine 60 in D1 and lysine 191 in D2 with sites on LRP1 to form a bivalent D1D2/LRP1 complex. When lysine 60 and 191 are both mutated to alanine, the binding of D1D2 to LRP1 is ablated. Our data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor.
  • Posted in Journal of Biological Chemistry, Publications
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