Research articles

Assisted by 3,800 chemical bioactivities, a bioinformatic analysis explores the inter-relatedness of over 170 kinases and generates a kinase interaction map based on sequence and ligand-binding activity that challenges the robustness of drug interaction networks.

The mechanisms and molecules involved in controlling biomineral formation remain unclear, though several proteins have been implicated in the process. Examination of crayfish now surprisingly points to upregulated glycolytic metabolites as playing a critical role in stabilizing amorphous calcium carbonate.

RNase T is a 3′-to-5′ exonuclease involved in RNA maturation pathways. Biochemical and three-dimensional structures of RNase T in complex with single- or double-stranded DNA reveal mechanisms of substrate selection and catalysis by this nuclease.

Single-molecule FRET experiments monitoring AMPA receptor dynamics reveal the energy landscape that the receptor samples and establish that agonists control the level of activation by modulating the fraction of protein in the closed-cleft conformation.

Triptolide is a bioactive natural product isolated from plants used in traditional Chinese medicine. A target identification approach shows that triptolide modulates RNA transcription and nucleotide excision repair by covalent binding to the XPB subunit of the transcription factor TFIIH.

The geometric relationship between the two protein degradation signals of proteasome substrates, the polyubiquitin chain and the unfolded region, is dictated by the locations of their recognition sites on the proteasome.

Feeding of modified carbohydrates has previously led to metabolic incorporation of these compounds into cellular glycans. Now the strategic use of a thiol analog that can be converted into an activated sugar but not incorporated into glycans provides a potent intracellular glycosyltransferase inhibitor.

Antibody glycans play important biological roles, but these functions are hard to reconcile with the current picture of carbohydrates tightly bound to the protein surface. Advanced NMR techniques and chemoenzymatic labeling strategies now point to large dynamic motions in these glycan chains.

Radical SAM enzymes are famous for catalyzing chemically diverse reactions. A mechanistic investigation of NosL, responsible for functionalizing the indole precursor of nosiheptide, now shows that this enzyme catalyzes an unusual fragmentation-recombination reaction that is tolerant to non-natural halogen substituents.

Random and targeted mutagenesis of serum paraoxonase, coupled with the development of a screen that allows detection of enzymatic activity against the toxic isomer of cyclosarin, yielded a mutant enzyme capable of protecting mice from a lethal dose of this dangerous nerve agent.

The structural revision of sublancin, previously thought to be a lantibiotic, instead reveals an unusual S-linked carbohydrate that is installed by a glycosyl transferase specific for thiols but promiscuous in its sugar substrates.

Ubiquitylated histone H2B (uH2B) is a known chromatin modification involved in transcription. Analysis of nucleosome arrays containing chemically synthesized uH2B proteins revealed that this posttranslational modification impairs chromatin fiber compaction and increases its accessibility through a mechanism distinct from other chromatin marks.