An intraresidue H-bonding motif in selenocysteine and cysteine, revealed by gas phase laser spectroscopy and quantum chemistry calculations
Résumé
Models of protein chains containing a seleno-cysteine (Sec) residue have been investigated by gas phase
laser spectroscopy in order to document the effect of the H-bonding properties of the SeH group in the
folding of the Sec side chain, by comparison with recent data on Ser- and Cys-containing sequences.
Experimental data, complemented by quantum chemistry calculations and natural bonding orbital (NBO)
analyses, are interpreted in terms of the formation of a so-called 5g intra-residue motif, which bridges
the acceptor chalcogen atom of the side chain to the NH bond of the same residue. This local
structure, in which the O/S/Se atom is close to the plane of the N-terminal side amide, is constrained
by local backbone-side chain hyperconjugation effects involving the S and Se atoms. Theoretical
investigations of the Cys/Sec side chain show that (i) this 5g motif is an intrinsic feature of these
residues, (ii) the corresponding H-bond is strongly non-linear and intrinsically weak, (iii) but enhanced by
g- and b-turn secondary structures, which promote a more favorable 5g H-bonding approach and
distance. The resulting H-bonds are slightly stronger in selenocysteine than in cysteine, but nearly
inexistent in serine, whose side chain in contrast behaves as a H-bonding donor. The modest spectral
shifts of the Cys/Sec NH stretches measured experimentally reflect the moderate strength of the
5g H-bonding, in agreement with the correlation obtained with a NBO-based H-bond strength indicator.
The evolution along the Ser, Cys and Sec series emphasizes the compromise between the several
factors that control the H-bonding in a hyperconjugation-constrained geometry, among them the chalcogen
van der Waals and covalent radii. It also illustrates the 5g H-bond enhancements with the Sec and Cys
residues favoured by the constraints imposed by the g- and b-turn structures of the peptide chain.
Origine : Fichiers éditeurs autorisés sur une archive ouverte