 |
PDBsum entry 3ddk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase, viral protein
|
PDB id
|
|
|
|
3ddk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of coxsackievirus b3 3dpol highlights the functional importance of residue 5 in picornavirus polymerases.
|
|
|
Authors
|
|
G.Campagnola,
M.Weygandt,
K.Scoggin,
O.Peersen.
|
|
|
Ref.
|
|
J Virol, 2008,
82,
9458-9464.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The crystal structure of the coxsackievirus B3 polymerase has been solved at
2.25-A resolution and is shown to be highly homologous to polymerases from
poliovirus, rhinovirus, and foot-and-mouth disease viruses. Together, these
structures highlight several conserved structural elements in picornaviral
polymerases, including a proteolytic activation-dependent N-terminal structure
that is essential for full activity. Interestingly, a comparison of all of the
picornaviral polymerase structures shows an unusual conformation for residue 5,
which is always located at a distortion in the beta-strand composed of residues
1 to 8. In our earlier structure of the poliovirus polymerase, we attributed
this conformation to a crystal packing artifact, but the observation that this
conformation is conserved among picornaviruses led us to examine the role of
this residue in further detail. Here we use coxsackievirus polymerase to show
that elongation activity correlates with the hydrophobicity of residue 5 and,
surprisingly, more hydrophobic residues result in higher activity. Based on
structural analysis, we propose that this residue becomes buried during the
nucleotide repositioning step that occurs prior to phosphoryl transfer. We
present a model in which the buried N terminus observed in all picornaviral
polymerases is essential for stabilizing the structure during this
conformational change.
|
|
|
|
|
|
|
