2-DIMENSIONAL H-1-NMR STUDY OF A TETRADECAPEPTIDE WITH THE CONSENSUS SEQUENCE ARG(5)-ASP-VAL-ARG-GLY - STRUCTURAL EFFECTS OF THE OUTSIDE SUBSTITUTION SER(12) BY ALA(12)
J. Riand et al., 2-DIMENSIONAL H-1-NMR STUDY OF A TETRADECAPEPTIDE WITH THE CONSENSUS SEQUENCE ARG(5)-ASP-VAL-ARG-GLY - STRUCTURAL EFFECTS OF THE OUTSIDE SUBSTITUTION SER(12) BY ALA(12), Journal of biomolecular structure & dynamics, 12(5), 1995, pp. 993-1008
Conformation of a tetradecapeptide with a RXVRG consensus sequence, Ar
g(5)-Asp-Val-Arg-Gly(9), found in several precursors of antibacterian
peptides, was investigated in dimethylsulfoxide solution by proton NMR
spectroscopy. Complete resonance assignments and conformational param
eters were obtained through correlated (COSY) and nuclear Overhauser (
NOESY) techniques. The (3)J(alpha H, beta H) coupling constants and th
e intramolecular NOE, NH...beta H, were used to analyse the conformers
around the C alpha-C beta bond and, in four cases, to obtain stereosp
ecific assignments. Use of restraints derived from NOE connectivities
and (3)J(NH, alpha H) coupling constants allows the determination of a
range of phi and psi dihedral angles for all the residues in the sequ
ence. The present NMR results provide favourable evidence for the form
ation of two bends in the consensus sequence of the tetradecapeptide.
The first one has most of the features of a Glu(4)- Val(7) beta-turn (
low temperature coefficient of the Val(7)NH chemical shift, Arg(5) alp
ha H...Val(7)NH and Asp(6)NH...Val(7)NH NOE correlations). The second
one exhibits only the Asp(6) alpha H...Arg(7)NH and Val(7)NH...Arg(8)N
H NOE interactions. These consensus sequence organizations proposed we
re confirmed by molecular modeling based on low potential energy struc
ture on the [4-9] fragment with high agreement of NOE data. Overall, t
he substitution of Ser(12) by Ala(12) shifts the conformation of the h
ydrophobic moiety [10-14] towards a quite random coil structure in thi
s fragment and strongly destabilizes the folded structures of the cons
ensus domain where only one NH (Val(7)) is solvent-shielded opposed to
three (Asp(6) to Arg(8)) in the [Ser(12)] tetradecapeptide. These con
formational changes could be related to the processing enzyme activiti
es on these model oligopeptides.