J. S. Fraser

MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation

This paper identifies N-lobe MET mutations in HPRCC that require ligand stimulation for activation, unlike kinase domain mutations, and shows their sensitivity to MET inhibitors.

Uncovering Protein Ensembles: Automated Multiconformer Model Building for X-ray Crystallography and Cryo-EM

This paper introduces enhanced qFit software for building multiconformer models from structural biology data, improving accuracy and usability.

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

This study characterizes the pH-specific enzymatic activity and ligand binding of mouse AMCase using structural and computational methods, revealing dual activity optima at pH 2 and 7.

Refinement of Multiconformer Ensemble Models from Multi-temperature X-ray Diffraction Data

This study refines multiconformer ensemble models from multi-temperature X-ray diffraction data of Proteinase K, revealing temperature-driven conformational changes and their functional implications.

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo

This study shows that mutating the SARS-CoV-2 NSP3 Mac1 domain reduces viral replication and pathogenesis in vivo.

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2

The paper computationally designs and experimentally validates potent inhibitors of the SARS-CoV-2 Nsp3 Macrodomain, identifying 160 ligands and 152 crystal structures with submicromolar affinity.

Mapping Protein Dynamics at High-Resolution with Temperature-Jump X-ray Crystallography

This study uses temperature-jump X-ray crystallography to observe atomic-scale protein motions in lysozyme, showing how vibrations evolve into functional movements and how inhibitors alter these dynamics.

Of Problems and Opportunities - How to Treat and How to not Treat Crystallographic Fragment-Screening Data

The paper shows that properly treated crystallographic fragment-screening data do not suffer from the criticisms raised by Jaskolski et al.

Molecular-Dynamics Simulation Methods for Macromolecular Crystallography

The paper applies molecular-dynamics simulations to macromolecular crystallography to refine protein structures and improve interpretation of electron density.

The mechanisms of catalysis and ligand binding for the SARS-CoV-2 NSP3 macrodomain from neutron and X-ray diffraction at room temperature

This study determines the crystal structures of SARS-CoV-2 NSP3 macrodomain using neutron and X-ray diffraction, revealing insights into its catalytic mechanism and ligand binding.

Ligand binding remodels protein side chain conformational heterogeneity

The paper measures conformational heterogeneity of protein side chains in ligand-bound and unbound states and finds that ligand binding increases flexibility in distant residues and correlates with inhibitor properties.

Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics

This study determines cryo-EM structures of oxazolidinone antibiotics bound to stalled ribosomes, revealing how alanine at the penultimate position enables context-specific inhibition.

Accurately positioning functional residues with robotics-inspired computational protein design

This paper introduces two computational methods for accurately positioning functional residues in proteins and validates them by redesigning enzyme active sites.

A counter-enzyme complex regulates glutamate metabolism in Bacillus subtilis

The paper identifies a counter-enzyme complex in Bacillus subtilis that regulates glutamate metabolism by inhibiting GudB activity, essential for growth under varying glutamate conditions.

Type 2 innate immunity regulates hair follicle homeostasis to control Demodex pathosymbionts

This study shows that type 2 innate immunity, via ILC2s, regulates hair follicle homeostasis and maintains commensal Demodex mite colonization.

Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance

This study uses directed evolution to identify Cfr variants that enhance rRNA methylation, revealing structural insights into antibiotic resistance mechanisms.

qFit 3: Protein and ligand multiconformer modeling for X-ray crystallographic and single-particle cryo-EM density maps

qFit 3 automates multiconformer modeling of dynamic proteins from X-ray and cryo-EM data, offering improved efficiency and accessibility.

Outcomes of the 2019 EMDataResource model challenge: validation of cryo-EM models at near-atomic resolution

The paper evaluates cryo-EM model quality using benchmark maps, showing high accuracy and reproducibility across 13 teams and recommending multiple metrics for model assessment.

Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray-derived conformational ensembles

This study uses X-ray crystallography to analyze enzyme active site positioning and motions, finding limited conformational changes and challenging existing catalytic mechanisms.

Expanding the space of protein geometries by computational design of de novo fold families

A computational method expands the structure space of designer proteins by systematically sampling loop-helix-loop geometries.

Evolution of an enzyme conformational ensemble guides design of an efficient biocatalyst

The paper uses X-ray crystallography to study conformational changes in an evolved enzyme, leading to the design of a more efficient biocatalyst by focusing on active-site mutations.

Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis

This study uses mix-and-inject XFEL crystallography to observe conformational changes in isocyanide hydratase during catalysis, showing how cysteine modification affects enzyme dynamics and function.

Liquid-like and rigid-body motions in molecular-dynamics simulations of a crystalline protein

This study uses MD simulations of a crystalline protein to analyze collective motions, finding liquid-like motions dominate inter-protein dynamics while rigid-body motions are present but subsumed within the overall liquid-like behavior.

Differences in the chitinolytic activity of mammalian chitinases on soluble and crystalline substrates

This study identifies mutations that enhance chitinase activity on oligomeric substrates but not crystalline chitin, highlighting the importance of using physiologically relevant substrates in enzyme engineering.

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals

This study compares serial X-ray crystallography and MicroED for determining structures from small macromolecular crystals, highlighting their strengths and challenges.

Computational design of a modular protein sense/response system

This paper designs modular protein sensors that respond to specific small molecule inputs using a computational strategy.

Co-occurring alterations in the RAS-MAPK pathway limit response to MET inhibitor treatment in MET exon 14 skipping mutation positive lung cancer

The paper identifies co-occurring RAS-MAPK pathway alterations in MET exon 14 skipping mutation positive lung cancers that limit response to MET inhibitors and suggests combining MET and MEK inhibitors to overcome resistance.

Temperature-Jump Solution X-ray Scattering Reveals Distinct Motions in a Dynamic Enzyme

This study uses temperature-jump X-ray scattering to analyze dynamic motions in cyclophilin A, revealing two distinct relaxation processes linked to substrate specificity and catalytic turnover.

qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps

qFit-ligand identifies unmodeled ligand conformations in crystal structures, revealing 29% of drug-like molecules exhibit conformational heterogeneity that could improve drug design.

Bringing Diffuse X-ray Scattering Into Focus

This paper discusses the potential of diffuse X-ray scattering to model protein motions with atomic detail by addressing its origins in protein crystallography.