title: Influence of serine in position i on conformation and dynamics of reverse turns.
abstract: NMR spectroscopy has been employed for the conformational analysis of the cyclic hexapeptide cyclo(-D-Pro1-Ala2-Ser3(Bzl)-Trp4-Orn5(Z)-Tyr 6-) with and without protecting groups on Ser3 and Orn5. This peptide sequence was derived from the active loop sequence of the alpha-amylase inhibitor Tendamistat (HOE 467). The aim was to investigate the role of serine in position i of a standard beta-turn on the conformation and stabilization of this turn. Based on distance and torsion constraints from 2D NMR spectroscopic measurements in DMSO-d6 solution, structure refinement was accomplished by restrained molecular dynamics (MD) simulations in vacuo and in DMSO. The analysis of both structures in solution reveals a considerable effect of the unprotected serine sidechain on the adjacent beta-turn conformation. While in the protected peptide with Ser3(Bzl) a beta II-turn is observed between Trp4 and Orn5, the deprotected compound reveals a beta I-turn in this region. The beta I-turn is stabilized by a backbone-sidechain hydrogen bond from Orn5N alpha H to Ser3O gamma. Comparisons with other NMR-derived solution structures of cyclic model peptides and in some protein structures from literature reveal a general structural motif in the stabilization of beta I-turns by serine in the i position through backbone-sidechain interactions.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Technical University of Munich, Garching, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Matter
authors.forename: G
authors.initials: G
authors.lastname: Gemmecker
authors.forename: H
authors.initials: H
authors.lastname: Kessler
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D010456:Peptides, Cyclic; D012694:Serine; D011392:Proline; D000516:alpha-Amylases; C030526:tendamistate