Volume 7 Issue 3, March 2011

Conformational transitions triggered by the binding of neurotransmitters open the gate of the ion channel domain of glutamate receptors, regulating the transmission of information through the nervous system. Using single-molecule fluorescence resonance energy transfer (smFRET), the agonist-binding domain of the GluA2 receptor, isolated in solution, is observed to interconvert among distinct large-scale conformational states.

Many proteins bear sugar residues that modulate their functionality. Clues about the energy landscape and accessibility of sugar conformations in immunoglobulin G will contribute to an understanding of the mechanistic and energetic aspects of glycobiology and immunology.

The radical SAM superfamily of enzymes provides, yet again, fertile ground for the discovery of amazing new biochemical transformations. Strong evidence is now presented for an unprecedented radical fragmentation-recombination of L-tryptophan to a derivative that is incorporated into the complex antibiotic nosiheptide, highlighting the versatility of radical mechanisms for complex biochemical reactions.

O-GlcNAc transferase is an essential protein catalyzing the O-GlcNAc modification of hundreds of intracellular proteins in higher eukaryotes. The structure of human O-GlcNAc transferase represents a leap in our understanding of the catalytic mechanism and recognition of protein substrates.

The nonlinear variant of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) microscopy, combines powerful Raman signal enhancement with several other advantages such as label-free detection and has been used to image various cellular processes including host-pathogen interactions and lipid metabolism.

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.

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.

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.

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.

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.