In silico assessment of phosphorylation and O-β-GlcNAcylation sites in human NPC1 protein critical for Ebola virus entry

摘要: Ebola is a highly pathogenic enveloped virus responsible for deadly outbreaks of severe hemorrhagic fever. It enters human cells by binding multifunctional cholesterol transporter Niemann–Pick C1 (NPC1) protein. Post translational modification (PTM) information NPC1 crucial to understand (EBOV) entry and action due changes in phosphorylation or glycosylation at the site. difficult costly experimentally assess this type interaction, so silico strategy was employed. Identification sites, including conserved residues that could be possible targets 21 predicted kinases followed interplay study between O-β-GlcNAc NPC1. Results revealed only 4 out 48 phosphosites exhibited activity. Predicted outcomes were integrated with residue conservation 3D structural information. Three Yin Yang sites located α-helix regions studied vertebrate mammalian species. Only one site S425 found β-turn region near N-terminus differ pig, mouse, cobra humans. The predictions suggest may not important attachment NPC1, whereas phosphosite 473 hence virus. This useful addressing further experimental studies therapeutic strategies targeting PTM events EBOV entry.