Potassium channels selectively conduct K + ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K + concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K + ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K + conduction. Crystallographic data are consistent with directly neighboring K + ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K + channels.

Protein biosynthesis depends on the availability of ribosomes, which in turn relies on ribosomal RNA production. In eukaryotes, this process is carried out by RNA polymerase I (Pol I), a 14-subunit enzyme, the activity of which is a major determinant of cell growth. Here we present the crystal structure of Pol I from Saccharomyces cerevisiae at 3.0 Å resolution. The Pol I structure shows a compact core with a wide DNA-binding cleft and a tightly anchored stalk. An extended loop mimics the DNA backbone in the cleft and may be involved in regulating Pol I transcription. Subunit A12.2 extends from the A190 jaw to the active site and inserts a transcription elongation factor TFIIS-like zinc ribbon into the nucleotide triphosphate entry pore, providing insight into the role of A12.2 in RNA cleavage and Pol I insensitivity to α-amanitin. The A49-A34.5 heterodimer embraces subunit A135 through extended arms, thereby contacting and potentially regulating subunit A12.2.

Chemists of all fields currently publish about 50 000 crystal structures per year, the vast majority of which are X‐ray structures. We determined two molecular structures by employing electron rather than X‐ray diffraction. For this purpose, an EIGER hybrid pixel detector was fitted to a transmission electron microscope, yielding an electron diffractometer. The structure of a new methylene blue derivative was determined at 0.9 Å resolution from a crystal smaller than 1×2 μm 2 . Several thousand active pharmaceutical ingredients (APIs) are only available as submicrocrystalline powders. To illustrate the potential of electron crystallography for the pharmaceutical industry, we also determined the structure of an API from its pill. We demonstrate that electron crystallography complements X‐ray crystallography and is the technique of choice for all unsolved cases in which submicrometer‐sized crystals were the limiting factor.

A specialized quantum area detector for electron diffraction studies makes it possible to solve the structure of small organic compound nanocrystals in non-cryo conditions by direct methods.

The ability of many copper metalloenzymes to activate O2 and transfer it to organic substrates has motivated extensive attention in the literature. Investigations focusing on synthetic analogues have provided a detailed understanding of the structures of potential intermediates, thereby helping to guide mechanistic studies. We report herein a crystallographically characterized synthetic Cu(II)2(μ-η(1):η(1)-O2) complex exhibiting cis-peroxo bonding geometry, known in iron chemistry but previously unobserved for copper. Detailed investigation by UV-vis, resonance Raman, and infrared spectroscopies provides evidence for a significantly diminished copper-oxygen interaction (ε ≈ 3000 M(-1) cm(-1), ν(Cu-O) = 437 cm(-1), ν(O-O) = 799 cm(-1)) relative to those in known 'coupled' Cu2O2 species, consistent with magnetic measurements which show that the peroxide mediates only weak antiferromagnetic coupling (-2J = 144 cm(-1)). These characteristics are comparable with those of a computationally predicted transition state for O2 binding to type 3 copper centers, providing experimental evidence for the proposed mechanism of O2 activation and supporting the biological relevance of the Cu(II)2(μ-η(1):η(1)-O2) cis-species. The peroxide bonding arrangement also allows binding of sodium cations, observed both in the solid state and in solution. Binding induces changes on an electronic level, as monitored by UV-vis spectroscopy (K(a) = 1700 M(-1)), reminiscent of redox-inactive metal binding by iron-oxygen species. The results presented highlight the analogous chemistry these reactive oxygen species undergo, with respect to both their mechanism of formation, and the molecular interactions in which they participate.