6VAR

61 nt human Hepatitis B virus epsilon pre-genomic RNA

Summary for 6VAR

• Entry DOI: 10.2210/pdb6var/pdb
• NMR Information: BMRB: 30701
• Descriptor: RNA (61-MER) (1 entity in total)
• Functional Keywords: non-coding rna, viral rna, rna
• Biological source: Hepatitis B virus
• Total number of polymer chains: 1
• Total formula weight: 19541.49

Authors

LeBlanc, R.M.,Kasprzak, W.K.,Longhini, A.P.,Abulwerdi, F.,Ginocchio, S.,Shields, B.,Nyman, J.,Svirydava, M.,Del Vecchio, C.,Ivanic, J.,Schneekloth, J.S.,Dayie, T.K.,Shapiro, B.A.,Le Grice, S.F.J. (deposition date: 2019-12-17, release date: 2020-12-30, Last modification date: 2024-05-15)

Primary citation

LeBlanc, R.M.,Kasprzak, W.K.,Longhini, A.P.,Olenginski, L.T.,Abulwerdi, F.,Ginocchio, S.,Shields, B.,Nyman, J.,Svirydava, M.,Del Vecchio, C.,Ivanic, J.,Schneekloth Jr., J.S.,Shapiro, B.A.,Dayie, T.K.,Le Grice, S.F.J.
Structural insights of the conserved "priming loop" of hepatitis B virus pre-genomic RNA.
J.Biomol.Struct.Dyn., :1-13, 2021

PubMed Abstract: Initiation of protein-primed (-) strand DNA synthesis in hepatitis B virus (HBV) requires interaction of the viral polymerase with a -acting regulatory signal, designated epsilon (ε), located at the 5'-end of its pre-genomic RNA (pgRNA). Binding of polymerase to ε is also necessary for pgRNA encapsidation. While the mechanistic basis of this interaction remains elusive, mutagenesis studies suggest its internal 6-nt "priming loop" provides an important structural contribution. ε might therefore be considered a promising target for small molecule interventions to complement current nucleoside-analog based anti-HBV therapies. An ideal prerequisite to any RNA-directed small molecule strategy would be a detailed structural description of this important element. Herein, we present a solution NMR structure for HBV ε which, in combination with molecular dynamics and docking simulations, reports on a flexible ligand "pocket", reminiscent of those observed in proteins. We also demonstrate the binding of the selective estrogen receptor modulators (SERMs) Raloxifene, Bazedoxifene, and a derivative to the priming loop.Communicated by Ramaswamy H. Sarma.

PubMed: 34155954
DOI: 10.1080/07391102.2021.1934544

Experimental method

SOLUTION NMR
SOLUTION SCATTERING