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
2013
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Sphingobium czechense sp nov., isolated from a hexachlorocyclohexane dump site
International Journal of Systematic and Evolutionary Microbiology, year: 2013, volume: 63, edition: Part 2, DOI
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The Effect of a Unique Halide-Stabilising Residue on the Catalytic Properties of Haloalkane Dehalogenase DatA from Agrobacterium tumefaciens C58
FEBS Journal, year: 2013, volume: 280, edition: 13, DOI
2012
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A Single Mutation in a Tunnel to the Active Site Changes the Mechanism and Kinetics of Product Release in Haloalkane Dehalogenase LinB
The Journal of Biological Chemistry, year: 2012, volume: 287, edition: 34, DOI
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Biochemical Characterization of a Novel Haloalkane Dehalogenase from a Cold-Adapted Bacterium
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, year: 2012, volume: 78, edition: 14, DOI
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CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures
PLoS Computational Biology, year: 2012, volume: 8, edition: 10, DOI
2011
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Biodegradation of 1,2,3-Trichloropropane
Year: 2011, type:
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Biochemical Characteristics of the Novel Haloalkane Dehalogenase DatA Isolated from the Plant Pathogen Agrobacterium tumefaciens C58.
Applied and Environmental Microbiology, year: 2011, volume: 77, edition: 5, DOI
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Biology and Bioinformatics
Year: 2011, type: Appeared in Conference without Proceedings
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CAVER 3.0: A Tool For Efficient Analysis Of Tunnels In Dynamic Protein Structures
Year: 2011, type: Appeared in Conference without Proceedings
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Computer-Assisted Enzyme Engineering by Modification of Tunnels, Channels and Gates.
Year: 2011, type: Appeared in Conference without Proceedings