Objective
Research objectives and content
Calmodulin is a calcium binding protein ( 148 residues) which can respond to changes in calcium concentration and cause activation of a number of important enzymes. High resolution structures have been reported for calmodulin complexed with target peptides from muscle myosin light chain kinases and calmodulin kinase II. These show the 'canonical' structure of a largely helical peptide embedded between the two domains of calmodulin. In the case of the phosphofructokinase, the regulation is unusual in that Ca2+ -calmodulin causes inhibition of the enzyme. Peptides from its target sequence for calmodulin binding have been synthesised and Circular Dichroism studies of their complexes with calmodulin suggest that these peptides have a different mode of interaction: the characterisation of this conformation could provide the first high resolution structural evidence of a target conformation other than the canonical form.
The object of this project is to determine the conformation of the bound peptides and the structure of their binding sites using multidimensional Nuclear Magnetic Resonance methods (including isotopic editing techniques) on calmodulin-peptide complexes. Labelled (15N/ 13C) calmodulin has already been prepared and a detailed set of multidimensional NMR experiments will be carried out to determine the constraints required to calculate the structures of the complexes.
Training content (objective, benefit and expected Impact)
Learning to use apply modern multidimensional Nuclear Magnetic Resonance techniques for examining protein-ligand complexes and for determining their structures. Methods for examining multiligand binding will be learnt. Circular Dichroism and other spectroscopic techniques will also be used. Links with industry / industrial relevance (22)
There is no direct links with industry but the project could provide overall improvements in methods of studying and understanding protein-ligand complexes in solution which could be of general interest to the pharmaceutical industry.
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 chemical sciences inorganic chemistry alkaline earth metals
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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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
NW7 1AA LONDON
United Kingdom
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.