STARPI4K

Structural targeting of PI4 kinases

Coordinatore	"USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I."    more  Organization address address: FLEMINGOVO NAM. 542/2 city: PRAHA 6 postcode: 16610 contact info Titolo: Ms. Nome: Jitka Cognome: Silerova Email: send email Telefono: 420220000000
Nazionalità Coordinatore	Czech Republic [CZ]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-03-01   -   2017-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	"USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I."  Organization address address: FLEMINGOVO NAM. 542/2 city: PRAHA 6 postcode: 16610 contact info Titolo: Ms. Nome: Jitka Cognome: Silerova Email: send email Telefono: 420220000000	CZ (PRAHA 6)	coordinator	100˙000.00

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 Obiettivo del progetto (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.'