Metabolic Feedback Circuits Provide Rapid Control of Metabolite Dynamics

January 8th, 2018 by Di Liu and Fuzhong Zhang

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.7b00342

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases

January 8th, 2018 by Matthew Jenner

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases

Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases, Published online: 08 January 2018; doi:10.1038/nchembio.2549

A combination of biochemical and structural techniques allows the characterization of a novel docking domain in polyketide synthases, which is structurally disordered and facilitates association of subunits at ketosynthase–dehydratase junctions.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases

Employing a biochemical protecting group for a sustainable indigo dyeing strategy

January 8th, 2018 by Tammy M Hsu

Employing a biochemical protecting group for a sustainable indigo dyeing strategy

Employing a biochemical protecting group for a sustainable indigo dyeing strategy, Published online: 08 January 2018; doi:10.1038/nchembio.2552

An environmentally friendly approach to indigo production is facilitated by the characterization of a plant indoxyl glucosyltransferase, which converts the unstable indoxyl precursor into indican by addition of a glucose protecting group.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Employing a biochemical protecting group for a sustainable indigo dyeing strategy

Na<sup>+</sup>-mimicking ligands stabilize the inactive state of leukotriene B<sub>4</sub> receptor BLT1

January 8th, 2018 by Tetsuya Hori

Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1

Na<sup>+</sup>-mimicking ligands stabilize the inactive state of leukotriene B<sub>4</sub> receptor BLT1, Published online: 08 January 2018; doi:10.1038/nchembio.2547

A structure of leukotriene B4 receptor BLT1 bound with a benzamidine-containing compound, BIIL260, reveals an inverse-agonist mechanism involving ligand binding in the sodium ion-centered water cluster adjacent to the conserved orthosteric site of class A GPCRs.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Na<sup>+</sup>-mimicking ligands stabilize the inactive state of leukotriene B<sub>4</sub> receptor BLT1

Next-Generation DNA-Functionalized Quantum Dots as Biological Sensors

January 4th, 2018 by Ganglin Wang, Zhi Li and Nan Ma

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.7b00887

Toxoplasma gondii disrupts {beta}1 integrin signaling and focal adhesion formation during monocyte hypermotility [Immunology]

January 2nd, 2018 by Joshua H. Cook, Norikiyo Ueno, Melissa B. Lodoen

The motility of blood monocytes is orchestrated by the activity of cell surface integrins, which translate extracellular signals into cytoskeletal changes to mediate adhesion and migration. Toxoplasma gondii is an intracellular parasite that infects migratory cells and enhances their motility, but the mechanisms underlying T. gondii-induced hypermotility are incompletely understood. We have investigated the molecular basis for the hypermotility of primary human peripheral blood monocytes and THP-1 cells infected with T. gondii. Compared to uninfected monocytes, T. gondii infection of monocytes reduced cell spreading and the number of activated β1 integrin clusters in contact with fibronectin during settling, an effect not observed in monocytes treated with LPS or E. coli. Furthermore, T. gondii infection disrupted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 (Y397) and Y925 and of the related protein proline-rich tyrosine kinase (Pyk2) at Y402. The localization of paxillin, FAK, and vinculin to focal adhesions and the colocalization of these proteins with activated β1 integrins were also impaired in T. gondii-infected monocytes. Using time-lapse confocal microscopy of THP-1 cells expressing eGFP-FAK during settling on fibronectin, we found that T. gondii-induced monocyte hypermotility was characterized by a reduced number of eGFP-FAK-containing clusters over time compared to uninfected cells. This study demonstrates an integrin conformation-independent regulation of the β1 integrin adhesion pathway, providing further insight into the molecular mechanism of T. gondii- induced monocyte hypermotility.

An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis

January 1st, 2018 by Andrea Chini

An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis

An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis, Published online: 01 January 2018; doi:10.1038/nchembio.2540

OPR3 is required to reduce the JA-Ile precursor OPDA. Analyses of JA levels in a loss-of-function opr3-3 mutant identified an OPR3-independent pathway for JA-Ile biosynthesis, based on OPDA conversion to 4,5-ddh-JA and reduction to JA by OPR2.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on An OPR3-independent pathway uses 4,5-didehydrojasmonate for jasmonate synthesis

Accessing chemical diversity from the uncultivated symbionts of small marine animals

January 1st, 2018 by Thomas E Smith

Accessing chemical diversity from the uncultivated symbionts of small marine animals

Accessing chemical diversity from the uncultivated symbionts of small marine animals, Published online: 01 January 2018; doi:10.1038/nchembio.2537

A combination of spectroscopy, metagenomics, and synthetic biology enables the characterization of the antiviral divamides, a class of lanthipeptide natural products in which even minor changes in structure lead to different biological activities.
  • Posted in Nat Chem Biol, Publications
  • Comments Off on Accessing chemical diversity from the uncultivated symbionts of small marine animals

Kinetic Characterization of Prenyl-Flavin Synthase from Saccharomyces cerevisiae

December 27th, 2017 by Nattapol Arunrattanamook and E. Neil G. Marsh

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.7b01131

Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017Utility and Limitations

December 26th, 2017 by Jonathan B. Baell and J. Willem M. Nissink

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.7b00903