4G93

CRYSTAL STRUCTURE OF THE HUMAN HEPATITIS B VIRUS T = 4 CAPSID, ADYW STRAIN, in COMPLEX WITH THE PHENYLPROPENAMIDE ASSEMBLY ACCELERATOR AT-130

Summary for 4G93

• Entry DOI: 10.2210/pdb4g93/pdb
• Related: 2G33 2G34
• Descriptor: Capsid protein, N-[(1E)-1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl]-4-nitrobenzamide (2 entities in total)
• Functional Keywords: virus, capsid, hepadnavirus, icosahedral, assembly effector, assembly accelerator, kinetic effector, phenylpropenamide, virus-inhibitor complex, virus/inhibitor
• Biological source: Hepatitis B virus subtype adyw (HBV-D)
• Cellular location: Virion : P03147
• Total number of polymer chains: 4
• Total formula weight: 68141.08

Authors

Katen, S.P.,Zlotnick, A. (deposition date: 2012-07-23, release date: 2013-07-24, Last modification date: 2024-02-28)

Primary citation

Katen, S.P.,Tan, Z.,Chirapu, S.R.,Finn, M.G.,Zlotnick, A.
Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure.
Structure, 21:1406-1416, 2013

PubMed Abstract: Hepatitis B virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly effectors. AT-130 causes tertiary and quaternary structural changes but does not disrupt capsid structure. AT-130 binds a hydrophobic pocket that also accommodates the previously characterized heteroaryldihydropyrimidine compounds but favors a unique quasiequivalent location on the capsid surface. Thus, this pocket is a promiscuous drug-binding site and a likely target for different assembly effectors with a broad range of mechanisms of activity. That AT-130 successfully decreases virus production by increasing capsid assembly rate without disrupting capsid structure delineates a paradigm in antiviral design, that disrupting reaction timing is a viable strategy for assembly effectors of HBV and other viruses.

PubMed: 23871485
DOI: 10.1016/j.str.2013.06.013

Experimental method

X-RAY DIFFRACTION (4.2 Å)