Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system

June 4th, 2018 by Tong Xiao

Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system

Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system, Published online: 04 June 2018; doi:10.1038/s41589-018-0062-z

Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.
  • Posted in Nat Chem Biol, Publications
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Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

June 4th, 2018 by Nan Wang

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme, Published online: 04 June 2018; doi:10.1038/s41589-018-0061-0

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.
  • Posted in Nat Chem Biol, Publications
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Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins

June 4th, 2018 by Jianchao Li

Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins

Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins, Published online: 04 June 2018; doi:10.1038/s41589-018-0082-8

Potent pan-Atg8 or GABARAP-selective inhibitory peptides derived from giant neuronal ankyrin-B and -G effectively block autophagy in cell cultures and in C. elegans spatiotemporally.
  • Posted in Nat Chem Biol, Publications
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Functional assignment of multiple catabolic pathways for <span class=”small-caps”>d</span>-apiose

June 4th, 2018 by Michael S. Carter

Functional assignment of multiple catabolic pathways for d-apiose

Functional assignment of multiple catabolic pathways for <span class="small-caps">d</span>-apiose, Published online: 04 June 2018; doi:10.1038/s41589-018-0067-7

A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Catalytic Bases and Stereocontrol in Lamiaceae Class II Diterpene Cyclases

May 30th, 2018 by Samuel Schulte, Kevin C. Potter, Cody Lemke, Reuben J. Peters

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00193

[ASAP] Sulfonium Ion Condensation: The Burden Borne by SAM Synthetase

May 30th, 2018 by Charles A. Lewis , Jr., Richard Wolfenden

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00477

[ASAP] Understanding Which Residues of the Active Site and Loop Structure of a Tyrosine Aminomutase Define Its Mutase and Lyase Activities

May 29th, 2018 by Gayanthi Attanayake, Tyler Walter, Kevin D. Walker

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00269

A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis

May 28th, 2018 by Xue Chen

A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis

A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis, Published online: 28 May 2018; doi:10.1038/s41589-018-0059-7

Although the conversion of (7S)-salutaridinol 7-O-acetate to thebaine can occur spontaneously, the identification of a thebaine synthase enzyme that catalyzes the reaction indicates how nature avoids the formation of labile hydroxylated byproducts.
  • Posted in Nat Chem Biol, Publications
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Arginine methylation of translocated in liposarcoma (TLS) inhibits its binding to long noncoding RNA, abrogating TLS-mediated repression of CBP/p300 activity [RNA]

May 21st, 2018 by Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa

Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS’s nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized. Herein, using various biochemical assays, we confirmed the earlier observations that TLS is methylated by protein arginine methyltransferase 1 (PRMT1) in vitro. The arginine methylation of TLS disrupted binding to pncRNA and also prevented binding of TLS to and inhibition of CBP/p300. This result indicated that arginine methylation of TLS abrogates both binding to pncRNA and TLS-mediated inhibition of CBP/p300 HAT activities. We also report that an arginine residue within the Arg–Gly–Gly domain of TLS, Arg-476, serves as the major determinant for binding to pncRNA. Either methylation or mutation of Arg-476 of TLS significantly decreased pncRNA binding and thereby prevented a pncRNA-induced allosteric alteration in TLS that is required for its interaction with CBP/p300. Moreover, unlike wildtype TLS, an R476A TLS mutant did not inhibit CCND1 promoter activity in luciferase reporter assays. Taken together, we propose the hypothesis that arginine methylation of TLS regulates both TLS–nucleic acid and TLS–protein interactions and thereby participates in transcriptional regulation.
  • Posted in Journal of Biological Chemistry, Publications
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ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing {alpha}-mannosidase-like protein 3 (EDEM3) [Protein Synthesis and Degradation]

May 21st, 2018 by Shangyu Yu, Shinji Ito, Ikuo Wada, Nobuko Hosokawa

Protein folding in the cell is regulated by several quality-control mechanisms. Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway. In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins. The mannosidases responsible for this process are ER mannosidase I and ER degradation–enhancing α-mannosidase–like proteins (EDEMs). However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro. Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3. This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain. In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor alpha locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3. On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
  • Posted in Journal of Biological Chemistry, Publications
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