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Probing the Role of the C-H···O Hydrogen Bond Stabilized Polypeptide Chain Reversal at the C-terminus of Designed Peptide Helices. Structural Characterization of Three Decapeptides

Aravinda, Subrayashastry and Shamala, Narayanaswamy and Bandyopadhyay, Abhishek and Balaram, Padmanabhan (2003) Probing the Role of the C-H···O Hydrogen Bond Stabilized Polypeptide Chain Reversal at the C-terminus of Designed Peptide Helices. Structural Characterization of Three Decapeptides. In: Journal of the American Chemical Society, 125 (49). pp. 15065-15075.

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Abstract

The structural characterization in crystals of three designed decapeptides containing a double D-segment at the C-terminus is described. The crystal structures of the peptides $Boc-Leu-Aib-Val-Xxx-Leu-Aib$ $-Val-^D Ala-^DLeu-Aib-OMe$, (Xxx = Gly 2, $^DAla 3$, Aib 4) have been determined and compared with those reported earlier for peptide 1 (Xxx = Ala) and the all L analogue Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe, which yielded a perfect right-handed \alpha-helical structure. Peptides 1 and 2 reveal a right handed helical segment spanning residues 1 to 7, ending in a Schellman motif with $^DAla(8)$ functioning as the terminating residue. Polypeptide chain reversal occurs at residue 9, a novel feature that appears to be the consequence of a C-H···O hydrogen bond between residue 4 $C^{\alpha}H$ and residue 9 CO groups. The structures of peptides 3 and 4, which lack the pro R hydrogen at the $C^{\alpha}$ atom of residue 4, are dramatically different. Peptide 3 adopts a right-handed helical conformation over the 1 to 7 segment. Residues 8 and 9 adopt $\alpha_L$ conformations forming a C-terminus type I' \beta-turn, corresponding to an incipient left-handed twist of the polypeptide chain. In peptide 4, helix termination occurs at Aib(6), with residues 6 to 9 forming a left-handed helix, resulting in a structure that accommodates direct fusion of two helical segments of opposite twist. Peptides 3 and 4 provide examples of chiral residues occurring in the less favored sense of helical twist; $^DAla(4)$ in peptide 3 adopts an $\alpha_R$ conformation, while $^LVal(7)$ in 4 adopts an $\alpha_L$ conformation. The structural comparison of the decapeptides reported here provides evidence for the role of specific C-H···O hydrogen bonds in stabilizing chain reversals at helix termini, which may be relevant in aligning contiguous helical and strand segments in polypeptide structures.

Item Type: Journal Article
Additional Information: The Copyright belongs to American Chemical Society.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 27 Apr 2006
Last Modified: 19 Sep 2010 04:26
URI: http://eprints.iisc.ernet.in/id/eprint/6527

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