C. Bernard et al., Solution structure of Ptul, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type, BIOCHEM, 40(43), 2001, pp. 12795-12800
Ptu1 is a toxin from the assassin bug Peirates turpis which has been demons
trated to bind reversibly the N-type calcium channels and to have lower aff
inity than the omega -conotoxin MVIIA. We have determined the solution stru
cture of Ptu1 by use of conventional two-dimensional NMR techniques followe
d by distance-geometry and molecular dynamics. The calculated structure of
Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that con
sists of a compact disulfide-bonded core from which four loops emerge. Anal
ysis of the 25 converged solutions indicates that the molecular structure o
f Ptu1 contains a 2-stranded antiparallel beta -sheet (residues 24-27 and 3
1-34) as the only secondary structure. The loop 2 that has been described t
o be critical for the binding of the toxin on the channel is similar in Ptu
1 and MVIIA. In this loop, the critical residue, Tyr13, in MVIIA is retriev
ed in Ptu1 as Phe13, but the presence of an acidic residue (Asp16) in Ptu1
could disturb the binding of Ptu1 on the channel and could explain the lowe
r affinity of Ptu1 toward the N-type calcium channel compared to the one of
MVIIA. Analysis of the electrostatic charge's repartition gives some insig
hts about the importance of the basic residues, which could interact with a
cidic residues of the channel and then provide a stabilization of the toxin
on the channel.