Featured
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Letter |
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
- Richard Possemato
- , Kevin M. Marks
- & David M. Sabatini
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Research Highlights |
Double hit from small molecules
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Comment |
Give memory-altering drugs a chance
The ethical challenges of memory-dampening drugs are likely to be manageable and the pay-offs considerable, says Adam Kolber.
- Adam Kolber
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Letter |
Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy
- Alex Sigal
- , Jocelyn T. Kim
- & David Baltimore
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Letter |
Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
- Christian Frezza
- , Liang Zheng
- & Eyal Gottlieb
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News |
Drug waste harms fish
Discharges from pharmaceutical factories contaminate rivers on three continents.
- Natasha Gilbert
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Letter |
N2O binding at a [4Cu:2S] copper–sulphur cluster in nitrous oxide reductase
- Anja Pomowski
- , Walter G. Zumft
- & Oliver Einsle
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Letter |
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
- Johannes Zuber
- , Junwei Shi
- & Christopher R. Vakoc
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Research Highlights |
Target for blocking cocaine
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Letter |
Oxysterols direct immune cell migration via EBI2
- Sébastien Hannedouche
- , Juan Zhang
- & Andreas W. Sailer
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Q&A |
Turning point: Christian Hackenberger
Bioorganic chemist Christian Hackenberger hopes to bring young investigators together in interdisciplinary collaborations.
- Katharine Sanderson
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News |
Cell signalling caught in the act
Receptor imaged in embrace with its G protein.
- Lizzie Buchen
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Article |
Crystal structure of the β2 adrenergic receptor–Gs protein complex
- Søren G. F. Rasmussen
- , Brian T. DeVree
- & Brian K. Kobilka
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Letter |
A two-step chemical mechanism for ribosome-catalysed peptide bond formation
- David A. Hiller
- , Vipender Singh
- & Scott A. Strobel
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Letter |
Selective killing of cancer cells by a small molecule targeting the stress response to ROS
- Lakshmi Raj
- , Takao Ide
- & Sam W. Lee
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News |
Mice with human livers deal with drugs the human way
'Humanized' mice could provide better assessment of drugs' toxicity for humans.
- Marian Turner
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Letter |
Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors
- Erkan Karakas
- , Noriko Simorowski
- & Hiro Furukawa
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Letter |
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
- Anita E. Autry
- , Megumi Adachi
- & Lisa M. Monteggia
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News |
Human cell becomes living laser
Jellyfish protein amplifies light in first biological laser.
- Zoë Corbyn
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Letter |
MicroRNAs 103 and 107 regulate insulin sensitivity
- Mirko Trajkovski
- , Jean Hausser
- & Markus Stoffel
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Research Highlights |
Bacterial chemical factories
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News & Views |
New lead for pain treatment
The synthesis of conolidine, a scarce, naturally occurring compound, has enabled the first studies of its pharmacological properties to be carried out. Excitingly, conolidine is a painkiller that seems to have an unusual mechanism of action.
- Sarah E. Reisman
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News |
Compound offers pain relief without the complications
The synthesis of a natural pain reliever could lead to an analgesic without serious side effects.
- Philip Ball
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Letter |
Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation
- Guillaume Lebon
- , Tony Warne
- & Christopher G. Tate
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Letter |
Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria
- Chris R. Reisch
- , Melissa J. Stoudemayer
- & William B. Whitman
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News & Views |
Life imitates art
The biosynthetic route to a naturally occurring insecticide, spinosyn A, has been established. One of the enzymes involved might catalyse a reaction that, although widely used by chemists, has proved elusive in nature. See Letter p.109
- Wendy L. Kelly
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News & Views |
To the rescue of the failing heart
Heart failure is characterized by weakened contractions of heart muscle. A drug that directly activates the key force-generating molecule in this muscle may be a valuable tool to strengthen the failing heart.
- Donald M. Bers
- & Samantha P. Harris
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Letter |
Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn A
- Hak Joong Kim
- , Mark W. Ruszczycky
- & Hung-wen Liu
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Research Highlights |
Antibiotics aided by other drugs
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News & Views |
How two amino acids become one
Twenty amino acids form the basis of all proteins, but another two genetically encoded amino acids have also been discovered. The biosynthesis of one of these, pyrrolysine, has now been elucidated. See Letter p.647
- Stephen W. Ragsdale
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News |
Dying for a long life
A chemical that stains Alzheimer's-associated proteins may help cells to cope with toxic trash.
- Ewen Callaway
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Letter |
The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine
Pyrrolysine is the twenty-second naturally occurring amino acid, and it is required for the formation of methane from methylamines. Pyrrolysine is the last remaining natural amino acid with a poorly characterized biosynthetic pathway. Here it is shown that the radical SAM protein PylB converts lysine to 3-methylornithine, which then undergoes a PylC-catalysed condensation with another lysine to generate a product that is oxidized by PylD to generate pyrrolysine.
- Marsha A. Gaston
- , Liwen Zhang
- & Joseph A. Krzycki
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Letter |
A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK
- Damian F. Brennan
- , Arvin C. Dar
- & David Barford
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Feature |
Chemistry: Enzyme expertise
Biocatalysis specialists are in high demand in industry.
- Katharine Sanderson
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Research Highlights |
Tagging the TB bacterium
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Letter |
The structural basis of agonist-induced activation in constitutively active rhodopsin
This study solves the X-ray crystal structure of a constitutively active mutant of rhodopsin, a G-protein-coupled receptor, bound to a peptide derived from the C-terminus of the G protein transducin. Comparison of this structure with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotational tilt of transmembrane helix 6, the critical conformational change that occurs upon activation.
- Jörg Standfuss
- , Patricia C. Edwards
- & Gebhard F. X. Schertler
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Letter |
Crystal structure of metarhodopsin II
Here the X-ray crystal structure of the metarhodopsin II intermediate of the photoreceptor rhodopsin is solved. Comparison of this structure with previously published structures enabled the proposal of how retinal translocation and rotation induce the conformational changes observed in this structure.
- Hui-Woog Choe
- , Yong Ju Kim
- & Oliver P. Ernst
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Article |
HDACs link the DNA damage response, processing of double-strand breaks and autophagy
The presence of DNA lesions is a clear signal that initiates the DNA damage response; however, the mechanisms that attenuate this response when repair has occurred are less clear. Here, deacetylation of Sae2 by Rpd3 and Hda1 is shown to be required for it to act on Mre11. When the role of Sae2 in resection is completed, it is acetylated by Gcn5 and degraded through an autophagic pathway. This work highlights links between DNA damage signalling, acetylation of repair factors, and autophagy mediated degradation of these factors.
- Thomas Robert
- , Fabio Vanoli
- & Marco Foiani
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Books & Arts |
Q&A: Perfumes preserved
Roman Kaiser, a chemist at the Givaudan Research Centre in Dübendorf, Switzerland, has recreated the scents of hundreds of rare and endangered plants in his laboratory, some of which he describes in his latest book. Here he explains how he preserves the smell of disappearing flora.
- Jascha Hoffman
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News |
Oil droplets mimic early life
Lack of genetic material no hindrance to life-like behaviour.
- Jo Marchant
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News |
Flies sniff out heavy hydrogen
Insects' ability to discriminate isotopes reignites debate over a controversial theory of olfaction.
- Philip Ball
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News |
Alzheimer's-disease probe nears approval
Imaging technique could help to resolve questions about brain plaques associated with the condition.
- Heidi Ledford
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News |
Salt-loving microbe forges its own path
The announcement of a third metabolic pathway raises possibility that there are more to be found.
- Tiffany O'Callaghan
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News & Views |
Catalytic detoxification
Protein engineering of an enzyme that catalytically detoxifies organophosphate compounds in the body opens up fresh opportunities in the search for therapeutic protection against nerve agents used in chemical warfare.
- Frank M. Raushel
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News & Views |
Binding the receptor at both ends
G-protein-coupled receptors initiate a wide range of signalling pathways in cells. It seems that both a G protein and an agonist molecule must bind to the receptors to persistently activate them. See Article p.175 & Letters p.236 & p.241
- Stephen R. Sprang
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Article |
Structure of a nanobody-stabilized active state of the β2 adrenoceptor
The X-ray crystal structure of the human β2 adrenergic receptor, a G-protein-coupled receptor, in an agonist-bound 'active' state is solved. Comparison of this structure with a previously published structure of the same GPCR in an inactive state indicates that minor changes in the binding pocket of the protein lead to major changes elsewhere — there is a large outward movement of the cytoplasmic end of one of the transmembrane segments and rearrangements of two other transmembrane segments. This structure provides insights into the process of agonist binding and activation.
- Søren G. F. Rasmussen
- , Hee-Jung Choi
- & Brian K. Kobilka
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Letter |
Nanoscale chemical tomography of buried organic–inorganic interfaces in the chiton tooth
Many biomineralized tissues (such as teeth and bone) are hybrid inorganic–organic materials whose properties are determined by their convoluted internal structures. Now, using a chiton tooth as an example, this study shows how the internal structural and chemical complexity of such biomaterials and their synthetic analogues can be elucidated using pulsed-laser atom-probe tomography.
- Lyle M. Gordon
- & Derk Joester
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Letter |
Structure and function of an irreversible agonist-β2 adrenoceptor complex
The X-ray crystal structure of the human β2 adrenergic receptor, a G-protein-coupled receptor (GPCR), covalently bound to a small-molecule agonist is solved. Comparison of this structure with structures of this GPCR in an inactive state and in an antibody-stabilized active state reveals how binding events at both the extracellular and intracellular surfaces stabilize the active conformation of the receptor. Molecular dynamics simulations suggest that the agonist-bound active state spontaneously relaxes to an inactive-like state in the absence of a G protein.
- Daniel M. Rosenbaum
- , Cheng Zhang
- & Brian K. Kobilka
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