MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

October 8th, 2018 by Louise Fets

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG, Published online: 08 October 2018; doi:10.1038/s41589-018-0136-y

High intracellular concentrations of the α-ketoglutarate analog N-oxalylglycine, owing to MCT2-mediated transport of its newly described prodrug MOG, inhibit multiple enzymes in glutamine metabolism and selectively kill MCT2-expressing cancer cells.
  • Posted in Nat Chem Biol, Publications
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New tricks for an old drug

October 8th, 2018 by Barbara S. Nelson

New tricks for an old drug

New tricks for an old drug, Published online: 08 October 2018; doi:10.1038/s41589-018-0137-x

The prodrug dimethyloxalylglycine (DMOG) is a well-known tool compound used to study hypoxia. New findings reveal that DMOG also inhibits glutamine metabolism and can be exploited to selectively kill some cancer cells, highlighting important caveats when using DMOG for hypoxia studies.

[ASAP] Characterization of Interactions and Phospholipid Transfer between Substrate Binding Proteins of the OmpC-Mla System

October 7th, 2018 by Bilge Ercan, Wen-Yi Low, Xuejun Liu, Shu-Sin Chng

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Biochemistry
DOI: 10.1021/acs.biochem.8b00897

Mechanistic basis for the evolution of chalcone synthase catalytic cysteine reactivity in land plants [Plant Biology]

October 5th, 2018 by Geoffrey Liou, Ying-Chih Chiang, Yi Wang, Jing-Ke Weng

Flavonoids are important polyphenolic natural products, ubiquitous in land plants, that play diverse functions in plants’ survival in their ecological niches, including UV protection, pigmentation for attracting pollinators, symbiotic nitrogen fixation, and defense against herbivores. Chalcone synthase (CHS) catalyzes the first committed step in plant flavonoid biosynthesis and is highly conserved in all land plants. In several previously reported crystal structures of CHSs from flowering plants, the catalytic cysteine is oxidized to sulfinic acid, indicating enhanced nucleophilicity in this residue associated with its increased susceptibility to oxidation. In this study, we report a set of new crystal structures of CHSs representing all five major lineages of land plants (bryophytes, lycophytes, monilophytes, gymnosperms, and angiosperms), spanning 500 million years of evolution. We reveal that the structures of CHS from a lycophyte and a moss species preserve the catalytic cysteine in a reduced state, in contrast to the cysteine sulfinic acid seen in all euphyllophyte CHS structures. In vivo complementation, in vitro biochemical and mutagenesis analyses, and molecular dynamics simulations identified a set of residues that differ between basal-plant and euphyllophyte CHSs and modulate catalytic cysteine reactivity. We propose that the CHS active-site environment has evolved in euphyllophytes to further enhance the nucleophilicity of the catalytic cysteine since the divergence of euphyllophytes from other vascular plant lineages 400 million years ago. These changes in CHS could have contributed to the diversification of flavonoid biosynthesis in euphyllophytes, which in turn contributed to their dominance in terrestrial ecosystems.

[ASAP] Distinct Differences in Structural States of Conserved Histidines in Two Related Proteins: NMR Studies of the Chemokines CXCL1 and CXCL8 in the Free Form and Macromolecular Complexes

October 1st, 2018 by Krishna Mohan Sepuru, Krishna Rajarathnam

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Biochemistry
DOI: 10.1021/acs.biochem.8b00756

[ASAP] Three-Step Isomerization of the Retinal Chromophore during the Anion Pumping Cycle of Halorhodopsin

October 1st, 2018 by Tsutomu Kouyama, Kunio Ihara, Kosuke Maki, Siu Kit Chan

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Biochemistry
DOI: 10.1021/acs.biochem.8b00631

[ASAP] Light at the End of the Amyloid Tunnel<subtitle>Published as part of the <italic toggle=”yes”>Biochemistry</italic> series “Biochemistry to Bedside”</subtitle>

September 30th, 2018 by Dennis J. Selkoe

Biochemistry
DOI: 10.1021/acs.biochem.8b00985

[ASAP] Reduced Occupancy of the Oxygen-Evolving Complex of Photosystem II Detected in Cryo-Electron Microscopy Maps

September 30th, 2018 by Jimin Wang, Krystle Reiss, Gary W. Brudvig, Victor S. Batista

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Biochemistry
DOI: 10.1021/acs.biochem.8b00609

[ASAP] A Nonheme Fe<sup>II</sup>/2-Oxoglutarate-Dependent Oxygenase Catalyzes a Double Bond Migration within a Dimethylallyl Moiety Accompanied by Hydroxylation

September 26th, 2018 by Huomiao Ran, Viola Wohlgemuth, Xiulan Xie, Shu-Ming Li

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00588
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[ASAP] Molecular Basis for Autocatalytic Backbone <italic toggle=”yes”>N</italic>-Methylation in RiPP Natural Product Biosynthesis

September 24th, 2018 by Chayanid Ongpipattanakul, Satish K. Nair

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00668
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