Volume 8 Issue 12, December 2012

The Methods section of original research papers will be published online only starting in 2013.

Post-translational modification of proteins by N-acetylglucosamine (O-GlcNAc) is carried out by a single glycosyltransferase, OGT. Two independent groups have generated structures of ternary complexes that elegantly illuminate substrate and product binding modes, and thus the overall reaction coordinate, but the respective authors differ in their choice of catalytic base.

A major determinant of the ion flux rate through acetylcholine receptors is a ring of five residues, four glutamates and a glutamine, at the channel's cytoplasmic mouth. The glutamates adopt alternate rotamer conformations so that only two directly affect channel conductance.

Combinatorial protein engineering based on structural data and the differential expression of alternate second receptor chains for interleukin-4 (IL-4) is used to modify and tune cellular specificity on primary human cells.

TsrM, a member of the radical SAM enzyme family, is shown to catalyze tryptophan methylation en route to thiostrepton A with the help of a methylcobalamin cofactor and without generating the canonical 5-deoxyadenosyl radical.

The identification of Escherichia coli ycfD and human MINA53 and NO66 as ribosomal amino acid hydroxylases defines a role for 2-oxoglutarate/iron-dependent oxygenases in translational regulation.

Riboswitches—RNA motifs that regulate gene expression in response to binding of specific ligands—have been identified for many small-molecule metabolites. An ATP-binding element in the ydaO mRNA of Bacillus subtilis provides the first example of an ATP-responsive riboswitch.

Understanding the reaction mechanism of OGT, responsible for O-GlcNAcylating various protein substrates, has been hampered by a lack of structural information. Snapshots of ternary complexes along the reaction coordinate now provide evidence for substrate participation in an electrophilic migration mechanism.

OGT modifies numerous proteins with O-GlcNAc, but the mechanism for this reaction has been difficult to define. Ternary crystal structures and activity assays with substrate analogs now provide evidence that the α-phosphate of the donor substrate is the catalytic base.

Only two of the four glutamates in the selectivity filter of the muscle acetylcholine receptor contribute to the single-channel conductance, with side chain torsional flexibility and microenvironment properties having a previously unrecognized role.

A kinase inhibitor based on a known type II inhibitor allosterically inhibits the RNase activity of IRE1α in vitro and in cells via the ATP-binding site in the kinase domain.

The creation and application of engineered constructs specific for one of two IL-4 coreceptors explain how immune signaling is limited by coreceptor concentration and establish specific roles for type II receptor–specific signaling in dendritic cell differentiation.

Potent, selective inhibitors reveal that DAGLβ is a principal 2-AG biosynthetic enzyme and regulates inflammatory processes in mouse peritoneal macrophages.