journal
MENU ▼
Read by QxMD icon Read
search

Nature Chemical Biology

journal
https://www.readbyqxmd.com/read/28319101/a-vibrio-cholerae-autoinducer-receptor-pair-that-controls-biofilm-formation
#1
Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost, Bonnie L Bassler
Quorum sensing (QS) is a cell-cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. In Vibrio cholerae, multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer-receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol (DPO). DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh)...
March 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28319100/metagenomic-discovery-of-polybrominated-diphenyl-ether-biosynthesis-by-marine-sponges
#2
Vinayak Agarwal, Jessica M Blanton, Sheila Podell, Arnaud Taton, Michelle A Schorn, Julia Busch, Zhenjian Lin, Eric W Schmidt, Paul R Jensen, Valerie J Paul, Jason S Biggs, James W Golden, Eric E Allen, Bradley S Moore
Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most prolific sources, marine sponges of the order Dysideidae, remains unidentified. Here, we report the discovery of PBDE biosynthetic gene clusters within sponge-microbiome-associated cyanobacterial endosymbionts through the use of an unbiased metagenome-mining approach...
March 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28319099/the-direct-role-of-selenocysteine-in-nifese-hydrogenase-maturation-and-catalysis
#3
Marta C Marques, Cristina Tapia, Oscar Gutiérrez-Sanz, Ana Raquel Ramos, Kimberly L Keller, Judy D Wall, Antonio L De Lacey, Pedro M Matias, Inês A C Pereira
Hydrogenases are highly active enzymes for hydrogen production and oxidation. [NiFeSe] hydrogenases, in which selenocysteine is a ligand to the active site Ni, have high catalytic activity and a bias for H2 production. In contrast to [NiFe] hydrogenases, they display reduced H2 inhibition and are rapidly reactivated after contact with oxygen. Here we report an expression system for production of recombinant [NiFeSe] hydrogenase from Desulfovibrio vulgaris Hildenborough and study of a selenocysteine-to-cysteine variant (Sec489Cys) in which, for the first time, a [NiFeSe] hydrogenase was converted to a [NiFe] type...
March 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28288109/in-silico-design-of-novel-probes-for-the-atypical-opioid-receptor-mrgprx2
#4
Katherine Lansu, Joel Karpiak, Jing Liu, Xi-Ping Huang, John D McCorvy, Wesley K Kroeze, Tao Che, Hiroshi Nagase, Frank I Carroll, Jian Jin, Brian K Shoichet, Bryan L Roth
The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin...
March 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28288108/structural-basis-of-protac-cooperative-recognition-for-selective-protein-degradation
#5
Morgan S Gadd, Andrea Testa, Xavier Lucas, Kwok-Ho Chan, Wenzhang Chen, Douglas J Lamont, Michael Zengerle, Alessio Ciulli
Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase-PROTAC-target species and its impact on target degradation selectivity remain elusive. We solved the crystal structure of Brd4 degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4(BD2))...
March 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28288107/decoding-cyclase-dependent-assembly-of-hapalindole-and-fischerindole-alkaloids
#6
Shasha Li, Andrew N Lowell, Sean A Newmister, Fengan Yu, Robert M Williams, David H Sherman
The formation of C-C bonds in an enantioselective fashion to create complex polycyclic scaffolds in the hapalindole- and fischerindole- type alkaloids from Stigonematales cyanobacteria represents a compelling and urgent challenge in adapting microbial biosynthesis as a catalytic platform in drug development. Here we determine the biochemical basis for tri- and tetracyclic core formation in these secondary metabolites, involving a new class of cyclases that catalyze a complex cyclization cascade.
March 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28288106/the-rrp4-exosome-complex-recruits-and-channels-substrate-rna-by-a-unique-mechanism
#7
Milos A Cvetkovic, Jan Philip Wurm, Maxime J Audin, Stefan Schütz, Remco Sprangers
The exosome is a large molecular machine involved in RNA degradation and processing. Here we address how the trimeric Rrp4 cap enhances the activity of the archaeal enzyme complex. Using methyl-TROSY NMR methods we identified a 50-Å long RNA binding path on each Rrp4 protomer. We show that the Rrp4 cap can thus simultaneously recruit three substrates, one of which is degraded in the core while the others are positioned for subsequent degradation rounds. The local interaction energy between the substrate and the Rrp4-exosome increases from the periphery of the complex toward the active sites...
March 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28263965/l-2-hydroxyglutarate-production-arises-from-noncanonical-enzyme-function-at-acidic-ph
#8
Andrew M Intlekofer, Bo Wang, Hui Liu, Hardik Shah, Carlos Carmona-Fontaine, Ariën S Rustenburg, Salah Salah, M R Gunner, John D Chodera, Justin R Cross, Craig B Thompson
The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D-R- or L-S- enantiomer, each of which inhibits α-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase (IDH) produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via 'promiscuous' reduction of the alternative substrate αKG...
March 6, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28263964/total-rna-seq-to-identify-pharmacological-effects-on-specific-stages-of-mrna-synthesis
#9
Sarah A Boswell, Andrew Snavely, Heather M Landry, L Stirling Churchman, Jesse M Gray, Michael Springer
Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation...
March 6, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28263963/the-structure-of-a-nucleolytic-ribozyme-that-employs-a-catalytic-metal-ion
#10
Yijin Liu, Timothy J Wilson, David M J Lilley
The TS ribozyme (originally called "twister sister") is a catalytic RNA. We present a crystal structure of the ribozyme in a pre-reactive conformation. Two co-axial helical stacks are organized by a three-way junction and two tertiary contacts. Five divalent metal ions are directly coordinated to RNA ligands, making important contributions to the RNA architecture. The scissile phosphate lies in a quasihelical loop region that is organized by a network of hydrogen bonding. A divalent metal ion is directly bound to the nucleobase 5' to the scissile phosphate, with an inner-sphere water molecule positioned to interact with the O2' nucleophile...
March 6, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28244989/a-fully-automated-flow-based-approach-for-accelerated-peptide-synthesis
#11
Alexander J Mijalis, Dale A Thomas, Mark D Simon, Andrea Adamo, Ryan Beaumont, Klavs F Jensen, Bradley L Pentelute
Here we report a fully automated, flow-based approach to solid-phase polypeptide synthesis, with amide bond formation in 7 seconds and total synthesis times of 40 seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to those for standard-batch solid-phase peptide synthesis. At full capacity, this approach can yield tens of thousands of individual 30-mer peptides per year.
February 28, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28244988/the-arabidopsis-o-fucosyltransferase-spindly-activates-nuclear-growth-repressor-della
#12
Rodolfo Zentella, Ning Sui, Benjamin Barnhill, Wen-Ping Hsieh, Jianhong Hu, Jeffrey Shabanowitz, Michael Boyce, Neil E Olszewski, Pei Zhou, Donald F Hunt, Tai-Ping Sun
Plant development requires coordination among complex signaling networks to enhance the plant's adaptation to changing environments. DELLAs, transcription regulators originally identified as repressors of phytohormone gibberellin signaling, play a central role in integrating multiple signaling activities via direct protein interactions with key transcription factors. Here, we found that DELLA is mono-O-fucosylated by the novel O-fucosyltransferase SPINDLY (SPY) in Arabidopsis thaliana. O-fucosylation activates DELLA by promoting its interaction with key regulators in brassinosteroid- and light-signaling pathways, including BRASSINAZOLE-RESISTANT1 (BZR1), PHYTOCHROME-INTERACTING-FACTOR3 (PIF3) and PIF4...
February 28, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28244987/capzimin-is-a-potent-and-specific-inhibitor-of-proteasome-isopeptidase-rpn11
#13
Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L Mackinnon, Christian Perez, Yuyong Ma, Kyle P Carter, Sharon Colayco, Gavin Magnuson, Brock Brown, Kevin Nguyen, Stefan Vasile, Eigo Suyama, Layton H Smith, Eduard Sergienko, Anthony B Pinkerton, Thomas D Y Chung, Amy E Palmer, Ian Pass, Sonja Hess, Seth M Cohen, Raymond J Deshaies
The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11...
February 28, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28244986/a-new-genome-mining-tool-redefines-the-lasso-peptide-biosynthetic-landscape
#14
Jonathan I Tietz, Christopher J Schwalen, Parth S Patel, Tucker Maxson, Patricia M Blair, Hua-Chia Tai, Uzma I Zakai, Douglas A Mitchell
Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products are attractive for genome-driven discovery and re-engineering, but limitations in bioinformatic methods and exponentially increasing genomic data make large-scale mining of RiPP data difficult. We report RODEO (Rapid ORF Description and Evaluation Online), which combines hidden-Markov-model-based analysis, heuristic scoring, and machine learning to identify biosynthetic gene clusters and predict RiPP precursor peptides...
February 28, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28218913/ligand-promoted-protein-folding-by-biased-kinetic-partitioning
#15
Karan S Hingorani, Matthew C Metcalf, Derrick T Deming, Scott C Garman, Evan T Powers, Lila M Gierasch
Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28218912/engineering-fatty-acid-synthases-for-directed-polyketide-production
#16
Jan Gajewski, Floris Buelens, Sascha Serdjukow, Melanie Janßen, Niña Cortina, Helmut Grubmüller, Martin Grininger
In this study, we engineered fatty acid synthases (FAS) for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach. Along with exploring the synthetic capability of FAS, we aim to build a foundation for efficient protein engineering, with the specific goal of harnessing evolutionarily related megadalton-scale polyketide synthases (PKS) for the tailored production of bioactive natural compounds.
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28218911/expanding-the-product-portfolio-of-fungal-type-i-fatty-acid-synthases
#17
Zhiwei Zhu, Yongjin J Zhou, Anastasia Krivoruchko, Martin Grininger, Zongbao K Zhao, Jens Nielsen
Fungal type I fatty acid synthases (FASs) are mega-enzymes with two separated, identical compartments, in which the acyl carrier protein (ACP) domains shuttle substrates to catalytically active sites embedded in the chamber wall. We devised synthetic FASs by integrating heterologous enzymes into the reaction chambers and demonstrated their capability to convert acyl-ACP or acyl-CoA from canonical fatty acid biosynthesis to short/medium-chain fatty acids and methyl ketones.
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28192414/selective-in-vivo-metabolic-cell-labeling-mediated-cancer-targeting
#18
Hua Wang, Ruibo Wang, Kaimin Cai, Hua He, Yang Liu, Jonathan Yen, Zhiyu Wang, Ming Xu, Yiwen Sun, Xin Zhou, Qian Yin, Li Tang, Iwona T Dobrucki, Lawrence W Dobrucki, Eric J Chaney, Stephen A Boppart, Timothy M Fan, Stéphane Lezmi, Xuesi Chen, Lichen Yin, Jianjun Cheng
Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28192413/evolution-of-a-split-rna-polymerase-as-a-versatile-biosensor-platform
#19
Jinyue Pu, Julia Zinkus-Boltz, Bryan C Dickinson
Biosensors that transduce target chemical and biochemical inputs into genetic outputs are essential for bioengineering and synthetic biology. Current biosensor design strategies are often limited by a low signal-to-noise ratio, the extensive optimization required for each new input, and poor performance in mammalian cells. Here we report the development of a proximity-dependent split RNA polymerase (RNAP) as a general platform for biosensor engineering. After discovering that interactions between fused proteins modulate the assembly of a split T7 RNAP, we optimized the split RNAP components for protein-protein interaction detection by phage-assisted continuous evolution (PACE)...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28192412/akap-mediated-feedback-control-of-camp-gradients-in-developing-hippocampal-neurons
#20
Kirill Gorshkov, Sohum Mehta, Santosh Ramamurthy, Gabriele V Ronnett, Feng-Quan Zhou, Jin Zhang
Cyclic AMP (cAMP) and protein kinase A (PKA), classical examples of spatially compartmentalized signaling molecules, are critical axon determinants that regulate neuronal polarity and axon formation, yet little is known about micro-compartmentalization of cAMP and PKA signaling and its role in developing neurons. Here, we revealed that cAMP forms a gradient in developing hippocampal neurons, with higher cAMP levels in more distal regions of the axon compared to other regions of the cell. Interestingly, this cAMP gradient changed according to the developmental stage and depended on proper anchoring of PKA by A-kinase anchoring proteins (AKAPs)...
April 2017: Nature Chemical Biology
journal
journal
40837
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"