Spotlights pubs.acs.org/JACS
Spotlights on Recent JACS Publications
■
■
ANALYTICAL, BIOCHEMICAL, AND COMPUTATIONAL TOOLS ELUCIDATE K+ CHANNEL SELECTIVITY The KcsA potassium ion channel is one of the most well-studied ion channel proteins. The KcsA channel is found in the cell membrane of a soil bacterium and forms a highly potassium selective pore. The structure of the pore is conserved among prokaryotic and eukaryotic potassium ion (K+) channels therefore research on KcsA can provide insights into K+ channel function more broadly. Flow of ions through a K+ channel is controlled by the selectivity filter at the extracellular side of the pore and a gate at the cytoplasmic side. Researchers led by Francis Valiyaveetil and Martin T. Zanni use two-dimensional infrared (2D IR) spectroscopy, coupled with advanced biochemical methods and molecular dynamics simulations, to carefully probe the selectivity filter and the communication with the intracellular gate (DOI: 10.1021/jacs.7b01594). 2D IR spectroscopy reveals new insights: For example, the team observes that the constricted state of the selectivity filter established by two different means (opening of the intracellular gate or depleting K+), are not energetically or conformationally equivalent thereby revealing an hitherto unrecognized complexity in the conformational landscape of the selectivity filter. The study highlights how combining biochemical, analytical, and computational techniques can make for a powerful approach in the investigation of ion binding channel proteins. Christine Herman, Ph.D.
SMALL PEPTIDES SELF-ASSEMBLE INTO GIANT NANOTUBE SHEETS One of the many goals of biomolecular chemists is to create supramolecular assemblies that rival the complexity of those found in nature. Progress toward this goal has only recently begun, and certain complex structures, such as microtubules and virus capsules, remain beyond that which can be designed from scratch in the lab. Now, James Nowick and co-workers demonstrate that a relatively small peptide can self-assemble to form macrocyclic sheets comparable in size and complexity to biomolecular machinery (DOI: 10.1021/jacs.7b03890). The team uses X-ray crystallography to take a close-up look at the sheets that have formed from a solution of a peptide composed of residues 16−22 of the β-amyloid peptide (Aβ). The analyses reveal that the sheets are made out of double-walled nanotubes, each with an inner diameter of 7 nm and an outer diameter of 11 nm. The peptide nanotubes pack together into a hexagonal lattice, resembling a honeycomb. The findings demonstrate that small amyloidogenic sequences can be used to create large nanostructures that may eventually serve as templates to form nanowires and other materials, and potentially lead to the discovery of new structures. Christine Herman, Ph.D.
■
POPPING OPEN THE BACTERIAL HOOD TO HARVEST POSSIBLE NEW ANTIBIOTICS In the search for new antibiotics, a lode of potential therapeutic compounds may be hiding under the bacterial hood. These are secondary metabolites encoded by “silent” gene clusters that are not expressed under normal bacterial growth conditions in the laboratory. If researchers could figure out what triggers the expression of these gene clusters, they could stimulate the production of many unknown natural products. Mohammad R. Seyedsayamdost and his colleagues previously designed a high-throughput screening method to identify compounds that activate these gene clusters by inserting a reporter gene encoding green fluorescent protein into the cluster of interest. Now they have applied the method to Streptomyces bacteria (DOI: 10.1021/jacs.7b02716). About half of the antibiotics currently in clinical use are derived from this genus. Through screening, the researchers find that expression of a silent gene cluster in Streptomyces albus is triggered by the antiparasitic compound ivermectin and the antibiotic etoposide. By using these compounds to induce expression of the cluster, they eventually isolate and determine the structures of 14 new secondary metabolites, which include a novel antifungal compound and several molecules that inhibit a cancer-associated protease. The work could be widely applied to find other metabolites expressed by the many other silent gene clusters in Streptomyces species. Deirdre Lockwood, Ph.D.
■
THE EXCEPTIONALISM OF (DI)OXYGEN The importance of the molecule of oxygen (O2) -more accurately called dioxygen -is well-recongnized. O2 is essential for many forms of life on earth, especially our own. Chemically, O2 is a fascinating molecule with surprising behavior. It is a diradical with a triplet ground state; thus, O2 is paramagnetic. Other diradicals are highly reactive, abstracting hydrogen atoms with ease and forming bonds to each other. Although oxygen has plenty of opportunity to undergo these reactions, it does not. O2 is kinetically quite stable and the barriers to the reaction of O2 with most molecules are high. On the other hand, oxygen reacts with practically every other element exothermically (notably, liquid O2 is a propellant for rockets). How can this be the case? Why does O2 have large barriers to undergoing reactions that (several steps down the line) liberate large amounts of energy? The explanation of oxygen's puzzling persistence is a large resonance stabilization energy, as explained in a theoretical study led by Weston Borden and Roald Hoffmann (DOI: 10.1021/ jacs.7b04232). Using careful analysis of thermodynamic data, coupled with calculations, the authors show that oxygen’s selfpreservation results from strong, resonance-stabilized, π bonding. On the other hand, oxygen’s weak σ bonding ultimately results in its reactions with most molecules being highly exothermic. Dalia Yablon, Ph.D. © XXXX American Chemical Society
A
DOI: 10.1021/jacs.7b06509 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
