Fluorescent Inhibitors as Tools To Characterize Enzymes: Case Study of the Lipid Kinase Phosphatidylinositol 4-Kinase III beta (PI4KB)

0474384 - ÚOCHB 2018 RIV US eng J - Článek v odborném periodiku
Humpolíčková, Jana - Mejdrová, Ivana - Matoušová, Marika - Nencka, Radim - Bouřa, Evžen
Fluorescent Inhibitors as Tools To Characterize Enzymes: Case Study of the Lipid Kinase Phosphatidylinositol 4-Kinase III beta (PI4KB).
Journal of Medicinal Chemistry. Roč. 60, č. 1 (2017), s. 119-127. ISSN 0022-2623. E-ISSN 1520-4804
Grant CEP: GA ČR GA15-09310S
GRANT EU: European Commission(XE) 333916 - STARPI4K
Institucionální podpora: RVO:61388963
Klíčová slova: crystal structure * replication * PI4KIII beta
Obor OECD: Organic chemistry
Impakt faktor: 6.253, rok: 2017

The lipid kinase phosphatidylinositol 4-kinase III beta (PI4KB) is an essential host factor for many positive-sense single-stranded RNA (+RNA) viruses including human pathogens hepatitis C virus (HCV), Severe acute respiratory syndrome (SARS), coxsackie viruses, and rhinoviruses. Inhibitor of PI4KB are considered to be potential broad-spectrum virostatics, and it is therefore critical to develop a biochemical understanding of the kinase. Here, we present highly potent and selective fluorescent inhibitors that we show to be useful chemical biology tools especially in determination of dissociation constants. Moreover, we show that the coumarin-labeled inhibitor can be used to image PI4KB in cells using fluorescence-lifetime imaging microscopy (FLIM) microscopy.
Trvalý link: http://hdl.handle.net/11104/0271445