Lipid‐induced Secondary Structures and Orientations of [Leu5]‐enkephalin: Helical and Crystallographic Double‐bend Conformers Revealed by IRATR and Molecular Modelling
作者:
Robert Schwyzer,
Panagiota Moutevelis‐Minakakis,
Shunsaku Kimura,
Hans‐Ulrich Gremlich,
期刊:
Journal of Peptide Science
(WILEY Available online 1997)
卷期:
Volume 3,
issue 1
页码: 65-81
ISSN:1075-2617
年代: 1997
DOI:10.1002/(SICI)1099-1387(199701)3:1<65::AID-PSC90>3.0.CO;2-Q
出版商: John Wiley&Sons, Ltd.
关键词: [Leu5]‐enkephalin;secondary structure;IRATR;MMX force field;bioactive conformation
数据来源: WILEY
摘要:
AbstractLipid‐induced secondary structures and orientations of the two enantiomeric [Leu5]‐enkephalins,L‐Tyr‐Gly‐Gly‐L‐Phe‐L‐Leu, andD‐Tyr‐Gly‐Gly‐D‐Phe‐D‐Leu, on flat multi‐bilayers of 1‐palmitoyl‐2‐oleoyl‐sn‐ glycero‐3‐phosphocholine (POPC) were examined with polarized attenuated total reflection IR (IRATR) spectroscopy and molecular mechanics procedures. The membrane‐bound peptides showed identical IR spectra in the amide I and II band regions that indicated membrane‐induced secondary structures and specific orientations of the non‐zwitterionic molecules. A Lorentzian band shape analysis based on second derivatives of the original curves and the observed band polarizations suggested the presence of helical structures (βIII‐and α‐turns), oriented more or less perpendicular to the membrane surface. Other folded structures,e.g.βI‐ and γ turns, were not excluded. Molecular modelling of non‐zwitterionic [Leu5]‐enkephalin with two βIII‐turns or an α‐turn resulted in essentially four low‐energy conformers containing (i) two βIII‐turns, (ii) one α‐turn, (iii) a βIII‐turn fused to an α‐turn, and (iv) a βIII‐turn fused to a βI‐turn as in the crystallographic molecular conformation described by Aubryet al. [Biopolymers28, 27–40 (1989)]. Zwitterionic [Leu5]‐enkephalin with two βIII‐turns collapsed to a C13turn (a distorted α‐ turn) bridged by a γI‐turn (v). The alignment of the amide I oscillators within the helical structures, (i), (ii) and (iii), and the double‐bend structures, (iv) and (v), explained the observed amide I and II polarizations. Differences between these and other lipid‐induced [Leu5]‐enkephalin conformers reported in the literature may be caused by the lipid polymorphism of the model membranes used. Possible implications of the new conformers for the molecular mechanism of opioid receptor selection are
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