Lipid-induced Secondary Structures and Orientations of [Leu5]-enkephalin: Helical and Crystallographic Double-bend Conformers Revealed by IRATR and Molecular Modelling
| Autor: | Hans-Ulrich Gremlich, Robert Schwyzer, Panagiota Moutevelis-Minakakis, Shunsaku Kimura |
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| Rok vydání: | 1997 |
| Předmět: |
Models
Molecular Spectrophotometry Infrared Protein Conformation Stereochemistry Infrared spectroscopy Crystallography X-Ray Biochemistry Protein Structure Secondary Turn (biochemistry) Membrane Lipids chemistry.chemical_compound Structural Biology Polymorphism (biophysics) Drug Discovery Molecule Computer Simulation Molecular Biology Conformational isomerism POPC Protein secondary structure Pharmacology Organic Chemistry General Medicine Crystallography Membrane chemistry Molecular Medicine Enkephalin Leucine |
| Zdroj: | Journal of Peptide Science. 3:65-81 |
| ISSN: | 1099-1387 1075-2617 |
| DOI: | 10.1002/(sici)1099-1387(199701)3:1<65::aid-psc90>3.0.co;2-q |
| Popis: | Lipid-induced secondary structures and orientations of the two enantiomeric [Leu5]-enkephalins, L-Tyr-Gly-Gly- L-Phe-L-Leu, and D-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 Aubry et al. [Biopolymers28, 27–40 (1989)]. Zwitterionic [Leu5]-enkephalin with two β III-turns collapsed to a C13 turn (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 discussed in terms of the membrane compartments theory. © 1997 European Peptide Society and John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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