314-800-4742
1701 Quincy Ave. Suite 21 Naperville, IL 60540
Email: info@apt-therapeutics.com
Protein Engineering FINAL
Technology
PROTEIN ENGINEERING
Optimizing Human Therapeutic Proteins
The immediate challenge of the genomics driven drug discovery process is to predict the precise biochemical function of the novel proteins needed to prioritize candidates for preclinical validation. The current solution relies on technologies for high-throughput sequence analysis and protein structure modeling to infer functional information. As demonstrated in the figure below, the existing approaches mainly classify the unknown protein to the level of protein superfamily and protein family, suggesting dubious functions. This level of functional annotation is not precise enough to properly choose the correct target, and in many instances incorrect protein leads are pursued wasting valuable resources and time.
Back
APT has developed a novel method that goes beyond the current capabilities of genomics companies allowing APT to assign precise biochemical function based on a knowledge of protein evolution, protein structure-function and enzyme mechanism and catalysis. This knowledge base, when combined with existing bioinformatics software, allows APT to distinguish the key differences among similar proteins, thus rapidly identifying the precise biochemical function of genes and the right therapeutic targets to pursue.
APT has developed a novel method that goes beyond the current capabilities of genomics companies allowing APT to assign precise biochemical function based on a knowledge of protein evolution, protein structure-function and enzyme mechanism and catalysis. This knowledge base, when combined with existing bioinformatics software, allows APT to distinguish the key differences among similar proteins, thus rapidly identifying the precise biochemical function of genes and the right therapeutic targets to pursue.
1. Chen R. (2001). Redesigning binding and catalytic specificities of enzymes. In Enzyme Technologies for
Pharmaceutical and Biotechnological Application. Kirst HA, Yeh WK and Zmijewski MJ eds. Academic Press (in
press).
2. Chen, R. (2001). Enzyme engineering: Rational design vs directed evolution. Trends Biotech 19: 13-14.
3. Miller S., Chen R., Karschnia E.J., Romfo C., Dean A. and LaPorte D.C. (2000) Locations of the regulatory sites
for isocitrate dehydrogenase kinase/phosphatase. J. Biol. Chem. 275: 833-839.
4. Chen R. (1999). A general strategy for enzyme engineering. Trends in Biotechnology 17, 344-345.
5. Chen R., Greer A. and Dean, A. D. (1997). Structural Constrains in Protein Engineering: The Coenzyme
Specificity of Escherichia coli Isocitrate Dehydroganase. Eur. J. Biochem. 250: 578-582.
6. Chen R., Greer A., Dean A.D. and Hurley L.H. (1997). Engineering secondary structure to invert coenzyme
specificity in isopropylmalate dehydrogenase. In Techniques in Protein Chemistry VIII. pp 809-816. Marshak
ed. Academic Press.
7. Chen R., Grobler J., Hurley J. H. and Dean A. D. (1996). Second-site supression of regulatory phosphorylation in
Escherichia coli isocitrate dehydrogenase. Protein Science. 5: 287-295.
8. Hurley J.H., Chen R. and Dean A. D. (1996). Determinants of cofactor specificity in isocitrate dehydrogenase:
structure of an engineered NADP>NAD specificity-reversal mutant. Biochemistry. 35: 5670-5678.
9. Chen R., Greer A. and Dean A. D. (1996). Redesigning secondary structure to invert coenzyme specificity in
isopropylmalate dehydrogenase. Proc. Natl. Acad. Sci. USA. 93: 12171-12176.
10. Chen R., Greer A. and Dean A. D. (1995). A highly active decarboxylating dehydrogenase with rationally
inverted coenzyme specificity. Proc. Natl. Acad. Sci. USA. 92: 11666-11670.