Project details

 

Evolution of substrate specificity in enzymes acting on xenobiotic compounds

Project Identification:IAA401630901
Project Period:1/2009 - 12/2013
Investor:link to a new windowAcademy of Sciences of the Czech Republic
MU Faculty/Unit:
Faculty of Science
MU Investigator:Prof. Mgr. Jiří Damborský, Dr.
Field:CE - Biochemistry (C - Chemistry)
EB - Genetics and molecular biology (E - Bio-science)
EE - Microbiology, virology (E - Bio-science)
Publications/Results:more
Keywords:evolution; enzymes; dehalogenation; multivariate statistics; substrate specificity; molecular modelling; virtual screening; QSAR and 3D QSAR
Annotation

The main objective of this project is to study evolution of substrate specificity in microbial enzymes acting on xenobiotic compounds. Selected model system, haloalkane dehalogenases, is suitable for this purpose since these enzymes act on recalcitrant compounds which have not been available in the biosphere until industrial revolution. Evolution will be studied recursively by quantitative characterization of the substrate specificity of modern haloalkane dehalogenases and their comparison with ancestral enzymes designed by phylogenetic inference and constructed by gene synthesis. The ultimate goal will be estimation of the level of functional overlap of individual protein subfamilies and dissecting molecular events leading to specialization of enzymes for efficient catalysis of their xenobiotic substrates. Various theoretical and experimental approaches will be employed to obtain appropriate biological material and collect data for testing of alternative evolutionary hypotheses.