Protein Engineering
Through our protein engineering expertise, we can modulate and optimize challenging
protein properties such as activity, affinity, selectivity, stability, resistance
to proteolytic degradation, and even improve protein expressability and solubility.
Bioinformatics
Our custom protein database helps us to gather protein-related information
and to capitalize on our accumulated experience.
Combined with classic bioinformatics tools, it allows us
to perform sequence analyses and alignments, molecular modelling or structural
predictions and/or optimize the choice of expression vectors, constructs
and production parameters.
Proprietary
Approaches
Besides custom protein engineering programmes, we also offer proprietary
engineering approaches.
Limited Proteolysis
By using a combination of limited proteolysis, chromatography and mass spectrometry
technologies, we can identify and separate individual functional domains
(minimal active fragment) within multi-domain proteins (recalcitrant proteins,
poorly soluble proteins, mix of folded proteins / locally unfolded proteins
/ unfolded proteins).
Protein Design
In order to increase the solubility, stability or ability
to crystallize of a given protein, we can use a protein compaction technology
based on the deletion of the protein’s non-essential floppy loops.
The resulting functional mini-protein will display a better therapeutic
value (therapeutic proteins, antigens) or a superior ability to crystallise
(target proteins).
This approach has been successfully applied by Protein’eXpert to both viral
antigens for vaccines development and anti-bacterial targets for drug discovery
applications.
Example
of Protein Engineering Application
Crystal structure of the PBP2x
Andréa Dessen, Nicolas Mouz, Elspeth Gordon, Julie Hopkins and Otto Dodeberg,
(2001) The journal of Chemistry, 276, 45106-45112.
Penicillin-binding proteins (PBPs) are the main targets for ß-lactam antibiotics,
such as penicillins and cephalosporins, in a wide range of bacterial species.
PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and
its modification is an essential step in the development of high level ß-lactam
resistance.
To understand such a mechanism, we used our protein engineering tools to
improve the solubility of the protein and to solve the X-Ray structure.