Thyroxine hormones visualized by the cryo-EM structure of bovine thyroglobulin

A study of natively iodinated bovine thyroglobulin demonstrates that structural details of biologically important chemical reactions can now be visualized by electron cryo-microscopy.

The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design

The predictive power of simulation has become embedded in the infrastructure of modern economies. The scientific and technical progress that needs to be made to improve the predictive power of biomolecular simulations and how this might be achieved are discussed.

Improving sampling of crystallographic disorder in ensemble refinement

Improvements to the ensemble refinement method are described and demonstrated. These improvements lead to more physically meaningful and interpretable macromolecular ensembles.

Monitoring reversion of hepatitis C virus-induced cellular alterations by direct-acting antivirals using cryo soft X-ray tomography and infrared microscopy

The study of cells replicating hepatitis C and treated with antiviral compounds by soft X-ray cryo tomography (cryo-SXT) and synchrotron-based infrared microscopy allows correlation of the viral structures resolved by the former with their chemical composition revealed by the latter. The results show the potential of cryo-SXT as a platform to determine the effectiveness of antiviral compounds in infected cells, guiding drug development at a preclinical level.

Redeployment of automated MrBUMP search-model identification for map fitting in cryo-EM

The modification of a crystallographic molecular-replacement pipeline for use in fitting search models to cryo-EM maps is described.

Ambiguities in and completeness of SAS data analysis of membrane proteins: the case of the sensory rhodopsin II–transducer complex

Ambiguities in and the completeness of SAS data analysis of membrane proteins (MPs) are considered here in the case of the sensory rhodopsin II–transducer complex solubilized in a detergent. The contribution of the detergent belt surrounding MPs is one of the main problems in SAS data analysis of MPs; the second problem addressed here is the influence of oligomerization polydispersity (which is a sufficiently common phenomenon for MPs) on the quality of SAS structural analysis.

Structure and metal-binding properties of PA4063, a novel player in periplasmic zinc trafficking by Pseudomonas aeruginosa

The structural and zinc-binding properties of PA4063, one of the periplasmic proteins expressed by Pseudomonas aeruginosa under zinc-deficient conditions, are presented. PA4063 has a noncanonical ferredoxin-like fold. Two zinc-binding sites with micromolar affinity are exposed and are located on the same face of the structure. Two histidine-rich loops, which are disordered in the apoprotein, contribute to zinc coordination in one of the sites. These findings strongly suggest a role for PA4063 in zinc trafficking, possibly acting as a metal chaperone or as a regulator of a transport system.

Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC/DeoR family

The first structural insight is provided into DNA recognition by the SorC/DeoR family of bacterial transcriptional regulators. Crystal structures of the DNA-binding domains of CggR and DeoR from Bacillus subtilis were determined in complexes with their DNA operators.

Crystallization, structural characterization and kinetic analysis of a GH26 β-mannanase from Klebsiella oxytoca KUB-CW2-3

The crystal structure of the β-mannanase KMAN from Klebsiella oxytoca KUB-CW2-3 and its mechanism of hydrolysis are reported.

Data- and diversity-driven development of a Shotgun crystallization screen using the Protein Data Bank

The REMARK280 field from the PDB was used to create an updated screen based on the most successful commercially available crystallization conditions. The new screen considers both the diversity of the screen along with the success of each of the conditions.

The structure of natively iodinated bovine thyroglobulin

Thyroglobulin is the precursor protein that serves as a substrate for thyroid hormone synthesis. Here, a three-dimensional cryoEM reconstruction of bovine thyroglobulin at an overall resolution of 2.6 Å is presented. The structure facilitates the definitive identification of thyroxine (acceptor) and dehydroalanine (donor) sites at two of the most evolutionarily conserved sites of hormone formation in vertebrates.

Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins

The crystal structures of SdgB and SdgA from Staphylococcus aureus provide functional and structural insights into the glycosylation mechanism in staphylococcal adhesion.

John D. Westbrook Jr (1957–2021)

John Westbrook is remembered.