Protein Crystallography

Co-founded by Nobel Laureate Prof. Huber in 1999, Proteros is a well established market-leading provider of structural biology services. We are working with more than 130 drug discovery companies and institutions worldwide. Over the last four years, our team has solved more than 1,500 protein-ligand structures (PLS) involving mainly small molecules, but also in addition biologics, covering over 180 different target proteins. Customers rely on our protein-ligand-structures particularly for very challenging targets. Not surprisingly, we often solve de-novo structures elucidating the protein fold and binding mode of new customer compounds.

Proteros’ crystallography science team expertise includes detailed target know-how, and in particular protein- and lipid kinases, proteases, membrane proteins, NA binding proteins, biologics and the cytokines.

For Gene-to-Structure projects you can rely on Proteros´ experience in having designed, produced and crystallized thousands of protein constructs. New constructs are designed by a knowledge-based design process, expressed in mammalian, insect or bacterial expression system and purified to homogeneity by our experienced in-house protein science department. For crystallographic initial screening we test up to 2000 crystallization conditions.

Proteros biophysical core facility supports the crystallization process by our proprietary Reporter Displacement Assay (RDA) and additional innovative biophysical technologies generating useful analytical information about functional expression, protein stability, correct folding, glycosylation patterns and ligand affinity. Where classical crystallization methods are limited, Proteros provides the solution with highly elaborated crystallization optimization technologies, the Free-Mounting-System (FMSTM), the FMS-IR-Laser and the FMS-PicoDropper.

Proteros Gallery Structures  (please click here to access Gallery Structure list) comprise a comprehensive list of established drug targets and off-target crystal systems, to be used as part of Proteros’ Protein X-ray Crystallography services in order to conduct protein-ligand structure analysis with customer compounds. These “off-the-shelf structures” enable fast and reliable turnaround times as Proteros has studied these crystal systems extensively and has established methodologies, protocols and SOPs for such systems. Accordingly, this allows an ideal basis for the determination of Protein-Ligand-Structures (PLS) with customer ligands of interest, as PLS can typically be generated in a time scale of a few weeks, instead of months.

Within the scope of Special Projects, customers have access to these proprietary technologies improving protein crystal quality, diffraction and ligand occupancy to obtain data of great additional value for the customer. Furthermore, single standard crystallographic services are offered, including initial crystallization, crystal optimization, data collection, structure solution, generation of movies to show any features of a given structure. Based on our high project success rate, customers tend to approach Proteros repeatedly and for even the most demanding protein targets. Diffraction and FMS-tests are performed on in house x-ray sources, data collection is mainly performed on a weekly / bi-weekly schedule at the industrial Synchrotron beamline (SLS-Swiss Light Source, PXII close to Zurich)  Frequent and flexible synchrotron access is ensured by a long term contract with SLS-TT-AG at Paul Scherrer Institute.

For companies engaged in Biologics drug discovery, Proteros offers structure determination using antibody/Fab + antigen material from customer with a high success rate.

Proteros Protein Crystallization Service, is meant for customers who initially want to test crystallizability of their protein as a prerequisite for a potential structure determination. This can easily be tested by using customer provided protein for 1000 initial crystallization trials and in-house x-ray diffraction testing.

For each project type we accelerate data processing and structure solutions via automated programs. The essential steps - like Ligand fitting and finalization of the structures - are performed manually by our experienced crystallographers.

 

Proteros Crystallography Service Process

Step1: Crystallization

Identification of crystallization hits and multi-dimensional optimization of crystal conditions:

 

Step 2: Application of Crystal Optimization Tools (FMS platform technology)

Customers have access through Proteros to its proprietary FMS technology platform for protein crystal optimization and improvement of Ligand occupancy:

  • Free-Mounting-System (FMSTM)

  • FMS-Laser

  • FMS-Pico-Dropper

 

The FMS is an established technology to improve the X-ray diffraction power  of protein crystals by control of humidity. Diffraction power is monitored online during the optimization process (rotating anode x-ray source) and crystals are conserved for synchrotron data collection by cryo freezing after optimization.

Furthermore by implementing the FMS-laser protein crystal can be dehydrated. These Technologies  open additional paths for success in customer Lead Discovery programs of our customers.

If ligand solubility and affinity are unfavorable and a protein-ligand complex cannot be formed by co-crystallization or classical soaking, the FMS-Pico-Dropper technology offers additional prospects as freely mounted protein crystals tolerate higher ligand concentrations. All customized crystal optimization technologies can enhance quality, speed and success rates.

 

Step 3: Protein Structure Analysis

For each project type we accelerate data processing and structure solution by automated programs. The essential steps - like Ligand fitting and finalization of the structures - are performed manually by our experienced crystallographers. Our experts strive for best possible data and interpretation; they verify every single structure carefully before delivery.

 

Proteros Success Examples

High resolution crystal structure analysis of most challenging targets, like GPCRs or ion channels with ligands is fully enabled at Proteros.

For further scientific questions regarding:

 

Please contact:

+49 89 700761-0

requests@proteros.com

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