X-ray Crystallography

Hear from one of our experts

Mark Elvin: Head of Cell Science

“Our talented crystallography team brings decades of experience in solving X-ray crystal structures over a wide range of different protein classes. Our proven expertise ranges from de-novo protein structure determination of challenging targets to delivering rapid turnaround protein-ligand complexes as well as managing X-ray based FBLG projects”.

Derek Ogg: Chief Scientific Officer and Protein Crystallographer

Crystallography workflow

A crystallography project can be an iterative project where individual stages need further optimisation based on the data obtained. For example, during an expression test we may observe a degradation product that suggests there is a more stable, more crystallisable portion of the target protein. We would then aim to confirm the domain boundaries and re-order a gene accordingly. To help manage this iterative approach, we break projects into stages with clear Stop/Go decision points between them.

Summary of what we provide

If what you need is not listed below then please contact us, as it is likely that one of our team has experience with the technique you require.

Protein Construct Design

  • Guided by bioinformatics and modelling.
  • Affinity tags to aid expression, purification and to meet end use requirements.
  • Chimeras, mutations, truncations, deletions to meet project needs.
  • IMPROvER software for membrane protein stability.
X-RAY CRYSTALLOGRAPHY

Crystallisation

  • Initial screening: both commercial and in-house designed sparse matrix screens.
  • Thermofluor screens – to explore buffers, pH, additives, substrates, cofactors, ions.
  • Co-crystallisation with tool compounds if required.
  • Fragment screening options including access to i04-1/XChem at Diamond for HTP.
  • Full automation of crystallisation and imaging in plate hotels.
    • Dragonfly to aid screen optimisation preparation.
    • Mosquito ultra-low volume liquid handling (reduces amount of protein required).
    • Formulatrix Rock Imager 1000 crystallisation plate hotel.
    • Rockmaker data analysis.

X-Ray data collection

  • Collection of high-quality, X-ray data at 3rd gen synchrotron light sources e.g. Diamond, ESRF, Soleil & SLS.
  • Regular reserved data collection slots.
  • Flexibility to book additional beamtime if faster turn-around times required.

Structure Determination

  • Via molecular replacement or de-novo phasing by Se-Met or SAD/MAD.
  • Multiple rounds of structure refinement.

X-ray Crystallography Resources

TitleContentCategoriesResources Typeshf:categorieshf:tax:resource_type
The key to delivering a FBDD project was optimising the crystal systemCase StudyMOREcase-study
Fragment Screening by Crystallography: An Alternative to High Throughput ScreeningCase StudyMOREcase-study
A Comparison of the Structural Techniques used at Sygnature Discovery: X-ray Crystallography, NMR and Cryo-EM, , , , BlogMOREcryo-em blog peak-favourites protein-nmr x-rayblog
The Role of Structural Biology in the Development of Biotherapeutics, , , , BlogMOREantibodies biotherapeutics cryo-em blog x-rayblog
Protein and the Planet 2: Directed Evolution of Proteins, , , BlogMOREcryo-em blog protein-nmr x-rayblog
Using Mass Spectrometry to Rapidly Facilitate Covalent Drug DiscoveryCase StudyMOREcase-study
AlphaFold for fast structural determination of a previously unsolved domainCase StudyMOREcase-study
Principal Scientist – Protein X-ray Crystallography, Company NewsMOREpeak-protein-news x-raycompany-news
Fragment Screening at Diamond Light SourceCompany NewsMOREx-raycompany-news
Steve’s Pymol Cheat SheetRead Steven Harborne’s recipe for creating great images with PyMol., ProtocolMOREfida x-rayprotocol
Optimising Endoglycosidase H Treatment of Proteins – All Thanks to Cauliflowers!Case StudyMOREcase-study
Beginners Guide to X-ray Data Processing, BlogMOREblog x-rayblog
RCSB PDB – Protein Structure DatabaseOnline resource powered by the Protein Data Bank providing structural information on the 3D shapes of proteins, nucleic acids, and …LinksMOREx-raylinks
A Beginner’s Guide to Macromolecular Crystallisation, BlogMOREpeak-favourites x-rayblog
Have Robots Taken My Job?, BlogMOREpeak-favourites x-rayblog
Peak Proteins – Solving G6b-BVideoMOREx-rayvideo
Determination of X-ray Crystal Structures of ERAP1 ComplexesWe were asked by Grey Wolf Therapeutics (in collaboration with Sygnature Discovery) to provide support for an endoplasmic reticulum aminopeptidase-1 …, BlogMOREpeak-favourites x-rayblog
Dr Derek Ogg’s Medicines Discovery Catapult Webinar, VideoMOREprotein-purification x-rayvideo
Do Structures of the Coronavirus Spike Protein Hold the Key to Winning?, BlogMOREprotein-purification x-rayblog
Preventing Protein Aggregation to Aid CrystallisationCase StudyMOREcase-study
Working with SPT Labtech’s Mosquito and DragonflyVideoMOREx-rayvideo
Producing Crystalline Protein-Ligand Complexes: Every Beautiful Partnership Starts with the Introduction.BlogMOREx-rayblog
How Was the Structure of G6b-B Determined?BlogMOREx-rayblog
Removing N-linked Oligosaccharides to Aid Protein CrystallisationCase StudyMOREcase-study
GPCR structural biology: from stubborn to stress-freeBlogMOREx-rayblog
The trials, tribulations and joy of protein crystallisationBlogMOREx-rayblog
What is Fragment-Based Lead Generation (FBLG)?Fragment-based lead generation (FBLG) is a very popular paradigm for early hit identification and lead generation and can be an …, BlogMOREpeak-favourites x-rayblog
Generation of a novel, secreted protein for structure determinationCase StudyMOREcase-study