Objective
Research objectives and content
The three-dimensional structure of the recombinant DHNA enzyme will be determined by protein X-ray crystallography. DHNA from E. Coli is a homooctamer with 123 amino acids and one Zn atom (anomalous scatter) per monomer. The enzyme cleaves a two-carbon segment from D-dihydroneopterin in an early step of folic acid biosynthesis. Folic acid derivatives serve as one-carbon donors in a wide variety of cellular reactions. Crystals of the protein diffracting to 2.1 A resolution have been already obtained by the applicant The structure will be solved using multiple wavelength anomalous dispersion (MAD) for phasing. Solvent flattening and molecular averaging will be important in Phase improvement. The refinement of the model structure will be done using least squares methods and fast fourier transform (FFT ) method.
The DHNA structure will help us to understand the fascinating biochemistry of pteridines and will be followed by inhibitory and mechanistic studies. Training content (objective, benefit and expected impact)
The objective of this training is to solve the structure of DHNA (dihydroneopterin aldolase). This is a new structure and will allow me to get further knowledge in the MIR techniques in which the host group has extensive experience, and in MAD techniques. The result of the investigation can have high impact in the design of a new generation of antibiotics that will inhibit DHNA.
Links with industry / industrial relevance (22)
Currently, links with the pharmaceutical industry do not exist but DHNA is potentially a very attractive target for new antibiotics against bacterial and parasitic diseases.
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 earth and related environmental sciences geology mineralogy crystallography
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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
82152 PLANEGG / KRAILLING
Germany
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