Project description
Enzymatic action explored
Enzymes are nature's catalysts, reducing the energy needed for reactions to occur, making them possible at rates that are physiologically relevant and without a lot of 'effort'. Of course, just as enzymes regulate the speed of reactions, the activity of enzymes must be regulated so that they are neither always active nor permanently inactivated. Allosteric regulation, regulation of an enzyme by a molecule that binds at a site other than the enzyme's active site, is common in nature and admired by synthetic biologists. Enhanced understanding of this molecular mechanism could be important to numerous fields from industrial chemistry to pharmaceuticals and biotechnology. The EU-funded DEAllAct project is investigating a natural enzyme system and its modulation. Insight will inform a model, a simulation tool that could predict which residues are of key importance to the binding of the regulator to its enzyme.
Objective
"Allosteric regulation of enzyme catalysis is widespread in nature and presents challenges and opportunities in synthetic biology. The enzyme ATP-phosphoribosyltransferase (ATPPRT) catalyses the first step in histidine biosynthesis, and is subject to complex allosteric inhibition by histidine. The short form of the enzyme, HisGS, is found in complex with a regulatory protein, HisZ. Such regulatory protein has a dual function: it allosterically enhances catalysis by HisGS, and it binds histidine and therefore mediates allosteric inhibition. The scientific aim of ""DEAllAct"" is to explore the design of a computational framework by combining state-of-the-art EVB/MM computational simulations and biophysical experimental studies to discover specific mutations at the protein-protein interface between HisGS and HisZ, that directly impact the transmission mechanism of the allosteric regulation. The fellow, Marina Corbella will carry out the project in Uppsala University under the supervision of Prof. Lynn Kamerlin who has extensive experience in computational chemistry and enzyme evolution. The first goal of ""DEAllAct"" is to elucidate the molecular details of the catalytic process of HisGS in the absence/presence of the regulatory protein HisZ via molecular dynamics simulations. Based on the information extracted from these simulations, a novel simulation tool will be developed to predict residues of key importance for binding interactions between the enzyme and the regulatory protein. Finally, the fellow will undergo a secondment at the University of St Andrews to test the hypothesis experimentally by introducing gain-of-function mutations on HisGS at the protein-protein interface to mimic the allosteric activation. Altogether, ""DEAllAct"" will provide the fellow with a highly competitive multidisciplinary profile by complementing her previous acquired expertise, putting her in a strong position to initiate her career as an independent and innovative research leader."
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 biological sciences synthetic biology
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences catalysis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences computer and information sciences software software applications simulation software
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
751 05 Uppsala
Sweden
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.