In This Issue

In this study the three-dimensional structure as well as internal and overall dynamics of the G3-subdomain of Initiation Factor 2 (IF2) from the bacterium Geobacillus stearothermophilus are studied. The folded core exposes charged regions that may interact with other IF2 subdomains or with ribosomal RNA. Flexible N- and C-termini that link G3 to its neighboring subdomains allow domain reorganization of IF2 on the ribosome during the assembly of a productive initiation complex. The finding of such internal dynamics in bacterial IF2 entails the presence of other ribosomal targets than previously recognized in the development of novel antibiotics.

Rv2074 from Mycobacterium tuberculosis belongs to a novel class of F₄₂₀H₂-dependent biliverdin reductases predominantly found in Actinobacteria. It reduces biliverdin-IXα to bilirubin-IXα, a potent antioxidant. Ahmed et al. have solved the X-ray crystal structure of Rv2074 in complex with its cofactor F₄₂₀, confirmed its reaction product as bilirubin-IXα, and used site-directed mutagenesis and molecular dynamics simulations to propose a similar reaction mechanism to the nicotinamide cofactor utilizing mammalian biliverdin reductases. As biliverdin-IXα is produced by macrophages during infection, its reduction to bilirubin-IXα by Rv2074 could play a role in protecting mycobacteria against oxidative stress, contributing to the survival of M. tuberculosis.

A handful of dominant preferred conformations of protein residues are identifiable as distinct populated regions on a Ramachandran plot. Each such cluster is commonly described as representing a single thermodynamic “basin.” Here, we argue that each such population is not homogeneous but is an aggregate of smaller populations that have distinct preferences and that are primarily distinguished by the conformations of their neighboring residues. We further provide evidence that the influence on a central residue of the conformations of its neighbors is greater than that of the identity of the neighboring residues, and we discuss how this information could be useful for improving modeling accuracy.

When the instant pulse of X-rays generated by a free electron laser (XFEL) hits a macromolecular crystal, electrons are stripped from its atoms, initiating the processes the will ultimately lead to its destruction. Earlier theoretical analyses suggested that the effects of these ionizations on structure factors could be ignored because they would be modest by comparison with R-factors of most protein structures deposited in the PDB (∼ 20%). Here it is shown that this conclusion is incorrect. Clear evidence of radiation damage can be obtained from the XFEL data sets available today in the PDB.