1eah

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spinqualitylabelsall models 1eah, resolution 2.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

PV2L COMPLEXED WITH ANTIVIRAL AGENT SCH48973

Overview

BACKGROUND: Polioviruses are human pathogens and the causative agents of, poliomyelitis. Polioviruses are icosahedral single-stranded RNA viruses, which belong to the picornavirus family, and occur as three distinct, serotypes. All three serotypes of poliovirus can infect primates, but only, type 2 can infect mice. The crystal structures of a type 1 and a type 3, poliovirus are already known. Structural studies of poliovirus type 2, Lansing (PV2L) were initiated to try to enhance our understanding of the, differences in host range specificity, antigenicity and receptor binding, among the three serotypes of poliovirus. RESULTS: The crystal structure of, the mouse neurovirulent PV2L complexed with a potent antiviral agent, SCH48973, was determined at 2.9 A resolution. Structural differences among, the three poliovirus serotypes occur primarily in the loop regions of the, viral coat proteins (VPs), most notably in the loops of VP1 that cluster, near the fivefold axes of the capsid, where the BC loop of PV2L is, disordered. Unlike other known structures of enteroviruses, the entire, polypeptide chain of PV2L VP4 is visible in the electron density and RNA, bases are observed stacking with conserved aromatic residues (Tyr4020 and, Phe4046) of VP4. The broad-spectrum antiviral agent SCH48973 is observed, binding in a pocket within the beta-barrel of VP1, in approximately the, same location that natural 'pocket factors' bind to polioviruses. SCH48973, forms predominantly hydrophobic interactions with the pocket residues., CONCLUSIONS: Some of the conformational changes required for infectivity, and involved in the control of capsid stability and neurovirulence in mice, may occur in the vicinity of the fivefold axis of the poliovirus, where, there are significant structural differences among the three poliovirus, serotypes in the surface exposed loops of VP1 (BC, DE, and HI). A surface, depression is located at the fivefold axis of PV2L that is not present in, the other two poliovirus serotypes. The observed interaction of RNA with, VP4 supports the observation that loss of VP4 ultimately leads to the loss, of viral RNA. A model is proposed that suggests dual involvement of the, virion fivefold and pseudo-threefold axes in receptor-mediated initiation, of infection by picornaviruses.

About this Structure

1EAH is a Protein complex structure of sequences from Human poliovirus 1 with MYR and SC4 as ligands. Full crystallographic information is available from OCA.

Reference

Structure of poliovirus type 2 Lansing complexed with antiviral agent SCH48973: comparison of the structural and biological properties of three poliovirus serotypes., Lentz KN, Smith AD, Geisler SC, Cox S, Buontempo P, Skelton A, DeMartino J, Rozhon E, Schwartz J, Girijavallabhan V, O'Connell J, Arnold E, Structure. 1997 Jul 15;5(7):961-78. PMID:9261087

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