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
2009
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HotSpot Wizard: a Web Server for Identification of Hot Spots in Protein Engineering.
NUCLEIC ACIDS RESEARCH, year: 2009, volume: 2009, edition: 37
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Chiral Aliphatic Hydroxy Compounds in Nature: a Review of Biological Functions and Practical Applications.
Collection of Czechoslovak chemical communications, year: 2009, volume: 74, edition: 7-8
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Pathways and Mechanisms for Product Release in the Engineered Haloalkane Dehalogenases Explored using Classical and Random Acceleration Molecular Dynamics Simulations.
JOURNAL OF MOLECULAR BIOLOGY, year: 2009, volume: 2009, edition: 00
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Quantitative Analyses of Substrate Specifity of Haloalkane Dehalogenase
Year: 2009, type: R&D Presentation
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Redesigning Dehalogenase Access Tunnels as a Strategy for Degrading an Anthropogenic Substrate.
NATURE CHEMICAL BIOLOGY, year: 2009, volume: 0000, edition: 5
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Studium dynamiky molekul vody v ústí tunelu haloalkándehalogenáz
Year: 2009, type: R&D Presentation
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Study of water molecule dynamics at the tunnel openings of haloalkane dehalogenase
Year: 2009, type: R&D Presentation