3ZFF

Human enterovirus 71 in complex with capsid binding inhibitor WIN51711

Summary for 3ZFF

• Entry DOI: 10.2210/pdb3zff/pdb
• Related: 3ZFE 3ZFG
• Descriptor: VP1, VP2, VP3, ... (5 entities in total)
• Functional Keywords: virus, inhibitor, capsid, picornavirus
• Biological source: HUMAN ENTEROVIRUS 71; More
• Cellular location: Picornain 3C: Host cytoplasm (By similarity). Protein 3B: Virion (By similarity): A9X4C2 A9X4C2 A9X4C2 A9X4C2
• Total number of polymer chains: 4
• Total formula weight: 94943.89

Authors

Plevka, P.,Perera, R.,Yap, M.L.,Cardosa, J.,Kuhn, R.J.,Rossmann, M.G. (deposition date: 2012-12-11, release date: 2013-03-27, Last modification date: 2023-12-20)

Primary citation

Plevka, P.,Perera, R.,Yap, M.L.,Cardosa, J.,Kuhn, R.J.,Rossmann, M.G.
Structure of Human Enterovirus 71 in Complex with a Capsid-Binding Inhibitor.
Proc.Natl.Acad.Sci.USA, 110:5463-, 2013

PubMed Abstract: Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-Å-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.

PubMed: 23509286
DOI: 10.1073/PNAS.1222379110

Experimental method

X-RAY DIFFRACTION (3.4 Å)