Project information
Evolution of substrate specificity in enzymes acting on xenobiotic compounds
- Project Identification
- IAA401630901
- Project Period
- 1/2009 - 12/2013
- Investor / Pogramme / Project type
-
Academy of Sciences of the Czech Republic
- Grants of distinctly investigative character focused on the sphere of research pursued at present particularly in the ASCR
- MU Faculty or unit
- Faculty of Science
- Keywords
- evolution; enzymes; dehalogenation; multivariate statistics; substrate specificity; molecular modelling; virtual screening; QSAR and 3D QSAR
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.
Publications
Total number of publications: 67
2011
-
Molekulární podstata působení organických rozpouštědel na strukturu a funkci haloalkandehalogenáz
Year: 2011, type: Appeared in Conference without Proceedings
-
Novosphingobium barchaimii LL02 sp. nov
Year: 2011
-
Paroxetine Metabolization and Cytochrome P450 2D6: Towards Predictive Models.
Year: 2011, type: Appeared in Conference without Proceedings
-
Sphingobium baderi LL03 sp. nov
Year: 2011
-
Sphingobium czechense LL01 sp. nov
Year: 2011
-
Stereoselectivity and Conformational Stability of Haloalkane Dehalogenase DbjA from Bradyrhizobium japonicum USDA110: The Effect of pH and Temperature.
FEBS Journal, year: 2011, volume: 278, edition: 15, DOI
-
Substrate Specificity of Haloalkane Dehalogenases
Biochemical Journal, year: 2011, volume: 435, edition: 435, DOI
2010
-
Biochemical and structural characterization of novel haloalkane dehalogenase DbeA from Bradyrhizobium elkani USDA94 possesing two halide binding sites
Year: 2010, type: Appeared in Conference without Proceedings
-
Development of an enzymatic fiber-optic biosensor for detection of halogenated hydrocarbons.
Analytical and Bioanalytical Chemistry, year: 2010, volume: 10, edition: 1007
-
Early Warning Biosensors for Detection of Chemical Warfare Agents.
CHEMICKE LISTY, year: 2010, volume: 104, edition: 104