Evidence of a Catalytic Dyad in F-Dependent Glucose-6-phosphate Dehydrogenase from .

F-dependent glucose-6-phosphate dehydrogenase (FGD) catalyzes the conversion of glucose-6-phosphate (G6P) to 6-phosphogluconolactone, using cofactor F as the hydride transfer acceptor. Our previous pH dependence studies suggested that E109 serves as an active site acid, donating a proton to the N-1 position of F, while leaving the role of H40 unanswered, which was previously suggested to serve as the active site base. This work utilizes thermodynamic and kinetic studies to elucidate additional mechanistic details concerning the roles of H40 and E13.

Poetry in motion: catching molecules in action.

Researchers have long sought to `see' proteins and other macromolecules in motion, to better understand their functions. Technological developments, notably advances in serial crystallography, are now making these dreams a reality, heralding a new era of kinetic crystallography.

Poly-γ-glutamylation of biomolecules.

Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F. Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show how poly-γ-glutamylation of folate and F by folylpolyglutamate synthases and γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L-glutamate onto growing γ-glutamyl chain termini.

Domain structure and cross-linking in a giant adhesin from the Mobiluncus mulieris bacterium.

Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed covalent intramolecular cross-links. While investigating the prevalence of such cross-links, a remarkable example was discovered in Mobiluncus mulieris, a pathogen associated with bacterial vaginosis. This organism encodes a putative adhesin of 7651 residues.

AlphaFold and the future of structural biology.

This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.

AlphaFold and the future of structural biology.

This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.

AlphaFold and the future of structural biology.

This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.

Identification of an immunodominant region on a group A T-antigen reveals temperature-dependent motion in pili.

Group A (GAS) is a globally important pathogen causing a broad range of human diseases. GAS pili are elongated proteins with a backbone comprised repeating T-antigen subunits, which extend from the cell surface and have important roles in adhesion and establishing infection. No GAS vaccines are currently available, but T-antigen-based candidates are in pre-clinical development.

Submission of structural biology data for review purposes.

The editors discuss the submission of structural biology data.

Submission of structural biology data for review purposes.

The editors discuss the submission of structural biology data.

Submission of structural biology data for review purposes.

The editors discuss the submission of structural biology data.

Inhibition of Indigoidine Synthesis as a High-Throughput Colourimetric Screen for Antibiotics Targeting the Essential Phosphopantetheinyl Transferase PptT.

A recently-validated and underexplored drug target in is PptT, an essential phosphopantetheinyl transferase (PPTase) that plays a critical role in activating enzymes for both primary and secondary metabolism. PptT possesses a deep binding pocket that does not readily accept labelled coenzyme A analogues that have previously been used to screen for PPTase inhibitors. Here we report on the development of a high throughput, colourimetric screen that monitors the PptT-mediated activation of the non-ribosomal peptide synthetase BpsA to a blue pigment (indigoidine) synthesising form in vitro.

Some lessons from COVID: science and communication.

Biomedical challenges such as the present COVID-19 pandemic require both good science and excellent communication between scientists and the general public. This underscores the importance of presenting our science in innovative ways that make it accessible to all.

Convergent pathways to biosynthesis of the versatile cofactor F.

Cofactor F is historically known as the methanogenic redox cofactor, having a key role in the central metabolism of methanogens, and archaea in general. Over the past decade, however, it has become evident this cofactor is more widely distributed across archaeal and bacterial taxa, suggesting a broader role for F in various metabolic and ecological capacities. In this article, we focus on the recent findings that have led to a deeper understanding of F biosynthetic enzymes and metabolites across microorganisms.

Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19.

Crystallography in its broadest sense has a crucial role to play in addressing the current COVID-19 pandemic. An outpouring of structural information on key viral proteins has resulted and importantly these data have immediately been shared with researchers round the world to speed the discovery of effective therapeutic agents.

Engineering of Group A Streptococcus Isopeptide Bonds into Immunoglobulin-Like Protein Domains.

Intramolecular isopeptide bonds, formed autocatalytically between Lys and Asn/Asp side chains, are widely present in the immunoglobulin-like domains of Gram-positive bacterial adhesins, including Group A Streptococcus, and confer considerable mechanical and chemical stability. These properties make them attractive for applications in biotechnology. Here, we detail the practical considerations that are involved in engineering isopeptide bonds into Ig-like proteins, including the choice of a site where bond-forming residues could be introduced and the appropriate methodology for mutagenesis.

Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19.

Crystallography in its broadest sense has a crucial role to play in addressing the current COVID-19 pandemic. An outpouring of structural information on key viral proteins has resulted and importantly these data have immediately been shared with researchers round the world to speed the discovery of effective therapeutic agents.

Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19.

Crystallography in its broadest sense has a crucial role to play in addressing the current COVID-19 pandemic. An outpouring of structural information on key viral proteins has resulted and importantly these data have immediately been shared with researchers round the world to speed the discovery of effective therapeutic agents.

Allosteric regulation of menaquinone (vitamin K) biosynthesis in the human pathogen .

Menaquinone (vitamin K) plays a vital role in energy generation and environmental adaptation in many bacteria, including the human pathogen (). Although menaquinone levels are known to be tightly linked to the cellular redox/energy status of the cell, the regulatory mechanisms underpinning this phenomenon are unclear. The first committed step in menaquinone biosynthesis is catalyzed by MenD, a thiamine diphosphate-dependent enzyme comprising three domains.

Regulation of human 4-hydroxy-2-oxoglutarate aldolase by pyruvate and α-ketoglutarate: implications for primary hyperoxaluria type-3.

4-hydroxy-2-oxoglutarate aldolase (HOGA1) is a mitochondrial enzyme that plays a gatekeeper role in hydroxyproline metabolism. Its loss of function in humans causes primary hyperoxaluria type 3 (PH3), a rare condition characterised by excessive production of oxalate. In this study, we investigated the significance of the associated oxaloacetate decarboxylase activity which is also catalysed by HOGA1.

The active site of the branched-chain amino acid biosynthesis enzyme dihydroxyacid dehydratase contains a 2Fe-2S cluster.

Iron-sulfur clusters are protein cofactors with an ancient evolutionary origin. These clusters are best known for their roles in redox proteins such as ferredoxins, but some iron-sulfur clusters have nonredox roles in the active sites of enzymes. Such clusters are often prone to oxidative degradation, making the enzymes difficult to characterize.

Findable Accessible Interoperable Re-usable (FAIR) diffraction data are coming to protein crystallography.

The policy of IUCr Journals on diffraction data is defined.

Findable Accessible Interoperable Re-usable (FAIR) diffraction data are coming to protein crystallography.

The policy of IUCr Journals on diffraction data is defined.

Findable Accessible Interoperable Re-usable (FAIR) diffraction data are coming to protein crystallography.

The policy of IUCr Journals on diffraction data is defined.

Findable Accessible Interoperable Re-usable (FAIR) diffraction data are coming to protein crystallography.

The policy of IUCr Journals on diffraction data is defined.