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Content archived on 2024-05-30

Structural targeting of PI4 kinases

Objective

Phosphatidyl inositol phosphates (PIPs) are biosynthesized from phosphatidyl inositol (PI) by the action of PI kinase. The phosphatidylinositol 4-phosphate (PI(4)P) is produced by the action of phosphatidylinositol 4-kinase (PI4K). PIPs are universal markers of intracellular membranes. Their precise spatial and temporal resolution control enables various protein machineries to operate in the correct location at the exact time. PI(4)P is the single most abundant mono phosphoinositide and is the marker of the Golgi and the trans-Golgi network (TGN). It has been reported to play a key role in membrane biogenesis, vesicular transport, lipid dynamics, and protein and lipid sorting in the TGN. Importantly, the replication of several plus RNA viruses, mainly the Hepatitis C virus (HCV), SARS, and poliovirus (PV) depend on PI(4)P. For instance, HCV hijacks PI4K III alpha to generate endoplasmatic reticulum (ER) derived membranous webs that are enriched in PI(4)P and where the replication of HCV takes place. The main goals of this proposal are (i.) to get structural insight into PI(4)P biosynthesis by solving crystal structure of the PI4K kinase domain and/or the full length enzyme (ii.) to solve the crystal structure of the kinase domain in complex with a small molecule inhibitor like the well known PIK93 (iii.) use the structural information to design novel small molecule inhibitors with higher affinity and specificity that could be used as antivirals.

Fields of science (EuroSciVoc)

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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.

Call for proposal

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FP7-PEOPLE-2012-CIG
See other projects for this call

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.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.
EU contribution
€ 100 000,00
Total cost

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.

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