Objective
We propose to study the importance of structural dynamics to enzymatic catalysis. This will utilise simplified model systems in which a variety of catalytically distinct mutants have been generated though directed evolution. This research will focus on whether changes to the conformational landscape of enzymes affect catalysis and how the structural scaffold can determine the optimum temperature for enzymatic activity. Two model systems will be used: (i) the lactate dehydrogenase family, chosen because it is the most heavily studied family with regards to thermophilicity; (ii) a designed Kemp elimination catalyst, chosen because it is the first example of an enzyme in which the evolution of the active site and structural scaffold has been decoupled. A synergistic experimental approach will be used to study the mutants generated through directed evolution: - Biophysics (temperature-controlled cryo-crystallography, incoherent neutron scattering, in-cristallo spectroscopy) and detailed data analysis (anisotropic and multiple crystallographic refinement) - Enzyme kinetics (temperature dependent kinetics and Arrhenius plots) - Computational simulation (normal mode analysis and molecular dynamics) This project will constitute, to our knowledge, one of the first attempts to apply directed evolution to the systematic analysis of the importance and evolution of pathways for dynamic conformational change in enzymatic catalysis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences computer and information sciences data science
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biophysics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences physical sciences optics spectroscopy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-IIF-2008
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
75794 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.