example, the structure of Norwalk virus polymerase
(PDB code 1SH3) was solved with two independent
molecules in the asymmetric unit, one of which is in
the in conformation while the other one is in the out
[30], and the structures of enterovirus 71 polymerase
show one instance of the loop in and two instances
of the loop out [26]. As in the poliovirus EC
structures, the loop is also in direct contact with the
template strand in the FMDV (foot-and-mouth
disease virus) 3Dpol–RNA complexes [25,27]. Additionally,
both the insertion of an extra serine after
Ser291 [39] and a Ser291Pro [17] mutation result in
loss of poliovirus infectivity, demonstrating the
importance of the loop for viral replication. Finally,
while the loop appears to be highly flexible based on
the heterogeneity seen in a comparison of multiple
polymerase structures [9], direct comparisons of the
conformations observed in multiple structures of any
one polymerase show that the loop has two
predominant conformations that largely correspond
to the in and out forms described in this work.