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Focus on Chemical Biology: Past, Present and Future

This special issue presents a collection of articles exploring the foundations of chemical biology, reviewing some of the major technical and conceptual advances of the last decade, and imagining the future of this vibrant field.

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Focus

Focus on Chemical Biology: Past, Present and Future

This special issue presents a collection of articles exploring the foundations of chemical biology, reviewing some of the major technical and conceptual advances of the last decade, and imagining the future of this vibrant field.

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Editorial

Focus on Chemical Biology: Past, Present and Future

Contemplating chemical biology p845

doi:10.1038/nchembio.465

In this special issue, Nature Chemical Biology takes a look at the past, present and future of chemical biology.


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Feature

Focus on Chemical Biology: Past, Present and Future

A decade of chemical biology pp847 - 854

Mirella Bucci, Catherine Goodman & Terry L Sheppard

doi:10.1038/nchembio.489

With insights from a panel of experts, the Nature Chemical Biology editors examine the evolution and current era of chemical biology.


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Commentaries

Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Informative diagnostics for personalized medicine pp857 - 859

Ryan C Bailey

doi:10.1038/nchembio.488

Some of the most celebrated triumphs of chemical biology are molecularly targeted therapeutics to combat human disease. However, a grand challenge looms as informative diagnostic strategies must be developed to realize the full impact of these promising pharmaceutical agents.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Transforming biosynthesis into an information science pp859 - 861

Travis S Bayer

doi:10.1038/nchembio.487

Engineering biosynthetic pathways to natural products is a challenging endeavor that promises to provide new therapeutics and tools to manipulate biology. Information-guided design strategies and tools could unlock the creativity of a wide spectrum of scientists and engineers by decoupling expertise from implementation.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Accessing new chemical space for 'undruggable' targets pp861 - 863

Sivaraman Dandapani & Lisa A Marcaurelle

doi:10.1038/nchembio.479

The synthesis and biological annotation of small molecules from underexplored chemical space will play a central role in the development of drugs for challenging targets currently being identified in frontier areas of biological research such as human genetics.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: RNA epigenetics? pp863 - 865

Chuan He

doi:10.1038/nchembio.482

Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: The chemistry of a dynamic genome pp866 - 868

Rahul M Kohli

doi:10.1038/nchembio.471

In the postsequencing era, chemical biology is uniquely situated to investigate genomic DNA alterations arising through epigenetic modifications, genetic rearrangements or active mutation. These transformations significantly expand nature's diversity and may profoundly alter our view of DNA's coding potential.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Beyond discovery: probes that see, grab and poke pp868 - 870

Joshua A Kritzer

doi:10.1038/nchembio.469

Chemical biology is now able to discover molecules that manipulate virtually any biological target or process. It remains a grand challenge to leverage these molecules into useful probes that can be used to address unsolved problems in biology.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Synthetic immunology to engineer human immunity pp871 - 872

David A Spiegel

doi:10.1038/nchembio.477

Rationally designing new strategies to control the human immune response stands as a key challenge for the scientific community. Chemical biologists have the opportunity to address specific issues in this area that have important implications for both basic science and clinical medicine.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Exploiting single-cell variation for new antibiotics pp873 - 875

Erick Strauss

doi:10.1038/nchembio.483

Variations between single members of a bacterial population can lead to antibiotic resistance that is not gene based. The future of effective infectious disease management might depend on a better understanding of this phenomenon and the potential to manipulate both it and microbial population dynamics in general.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Chassis cells for industrial biochemical production pp875 - 877

Claudia E Vickers, Lars M Blank & Jens O Krömer

doi:10.1038/nchembio.484

Hyper-performing whole-cell catalysts are required for the renewable and sustainable production of petrochemical replacements. Chassis cells—self-replicating minimal machines that can be tailored for the production of specific chemicals—will provide the starting point for designing these hyper-performing 'turbo cells'.


Focus on Chemical Biology: Past, Present and Future

Grand Challenge Commentary: Chemical transdifferentiation and regenerative medicine pp877 - 879

Bridget K Wagner

doi:10.1038/nchembio.472

The ability to alter cell identity with small molecules represents a powerful approach to restore biological function lost because of cellular deficiency. Developing this capability through advances in chemical biology could have an enormous impact on human health.


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News and Views

Chaperones: A story of thrift unfolds pp880 - 881

François Baneyx & Brent L Nannenga

doi:10.1038/nchembio.468

Although members of the Hsp70-DnaK family of heat shock proteins are involved in nearly all aspects of cell physiology, some mechanistic details of their mode of action remain obscure. A new substrate helps establish DnaK as an unfoldase that requires as little as five ATP molecules to drive the refolding of one protein.

See also: Article by Sharma et al.


Molecular probes: Getting lucky in the lysosome pp881 - 883

Ethan D Goddard-Borger, Tom Wennekes & Stephen G Withers

doi:10.1038/nchembio.470

Conjugation of a known, mechanism-based glycosidase inhibitor to sensitive fluorophores yielded unexpectedly potent and selective probes for quantifying active lysosomal glucocerebrosidase. These conjugates could prove to be invaluable tools for diagnosing and studying Gaucher disease.

See also: Article by Witte et al.


Glycobiology: Cellulose squeezes through pp883 - 884

Anne Endler, Clara Sánchez-Rodríguez & Staffan Persson

doi:10.1038/nchembio.480

The glucose-based polymer cellulose is of great biological and economical importance; however, little is known about how cellulose is synthesized. Now, structural estimates of one of the cellulose-synthesizing subunits in the bacterium Acetobacter xylinum help to explain the extrusion of the newly synthesized glucan chains.


Imaging: Visualizing a neuronal handshake pp885 - 886

Atsushi Miyawaki

doi:10.1038/nchembio.486

A new method to monitor interactions between cell surface proteins reveals that interaction of the neuronal cell surface adhesion proteins neurexin and neuroligin is increased at synapses during a stimulus or developmental activity. This increased activity-dependent surface density of neurexin–neuroligin complexes is subsequently required for maturation of synapses.


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Brief Communication

Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer pp887 - 889

Lisa M Miller Jenkins, David E Ott, Ryo Hayashi, Lori V Coren, Deyun Wang, Qun Xu, Marco L Schito, John K Inman, Daniel H Appella & Ettore Appella

doi:10.1038/nchembio.456

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The antiviral S-acyl-2-mercaptobenzamide thioester ejects an essential coordinated zinc ion from and induces aggregation and dysfunction of the HIV-1 nucleocapsid protein NCp7 via repetitive intracellular enzymatic acyl transfers, dependent on acetyl-CoA.


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Articles

Microscopic rotary mechanism of ion translocation in the Fo complex of ATP synthases pp891 - 899

Denys Pogoryelov, Alexander Krah, Julian D Langer, Özkan Yildiz, José D Faraldo-Gómez & Thomas Meier

doi:10.1038/nchembio.457

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Free-energy molecular dynamics simulations and high-resolution structural analysis of the c-ring of the F1Fo ATPase rotary motor, which mediates ion translocation, suggest conformational flexibility and reversible ion binding in the c-subunits, in an environment mimicking the a-subunit.


Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins pp900 - 906

Benjamin G Hoffstrom, Anna Kaplan, Reka Letso, Ralf S Schmid, Gregory J Turmel, Donald C Lo & Brent R Stockwell

doi:10.1038/nchembio.467

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Expression of a Huntington's-disease variant of huntingtin protein causes accumulation of the chaperone protein disulfide isomerase. This protein is the target of compounds obtained from screening for those that can alleviate cell death promoted by the mutant huntingtin, and represents a new connection between protein misfolding and cell death.


Ultrasensitive in situ visualization of active glucocerebrosidase molecules pp907 - 913

Martin D Witte, Wouter W Kallemeijn, Jan Aten, Kah-Yee Li, Anneke Strijland, Wilma E Donker-Koopman, Adrianus M C H van den Nieuwendijk, Boris Bleijlevens, Gertjan Kramer, Bogdan I Florea, Berend Hooibrink, Carla E M Hollak, Roelof Ottenhoff, Rolf G Boot, Gijsbert A van der Marel, Herman S Overkleeft & Johannes M F G Aerts

doi:10.1038/nchembio.466

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Fluorescent high-affinity activity-based probes used to monitor the activity and presence of active glucocerebrosidase in vitro and in vivo help in understanding Gaucher disease and its treatment with pharmacological chaperones.

See also: News and Views by Goddard-Borger et al.


The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase pp914 - 920

Sandeep K Sharma, Paolo De Los Rios, Philipp Christen, Ariel Lustig & Pierre Goloubinoff

doi:10.1038/nchembio.455

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Protein chaperones help misfolded proteins reach their native state, but the necessarily unstable substrates have complicated the analysis of chaperone function. A stable misfolded luciferase substrate now allows the determination of traditional enzyme parameters for the DnaK system, demonstrating that five cycles of unfolding and release are needed for one successful refolding event.

See also: News and Views by Baneyx & Nannenga


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Erratum

Erratum: Research Highlights p921

doi:10.1038/nchembio1210-921


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