7LIB

X-ray crystal structure of a cyclic peptide containing beta-2-microglobulin (63-69) and a gamma-methylornithine turn unit

Summary for 7LIB

• Entry DOI: 10.2210/pdb7lib/pdb
• Descriptor: Cyclic peptide ORD-TYR-LEU-LEU-PHI-TYR-THR-GLU-GMO-LYS-VAL-THR-MVA-THR-VAL-LYS (2 entities in total)
• Functional Keywords: turn unit, beta-2-microglobulin, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 2088.27

Authors

Wierzbicki, M.,Nowick, J.S.,Li, X. (deposition date: 2021-01-26, release date: 2021-08-11, Last modification date: 2023-11-15)

Primary citation

Li, X.,Sabol, A.L.,Wierzbicki, M.,Salveson, P.J.,Nowick, J.S.
An Improved Turn Structure for Inducing beta-Hairpin Formation in Peptides.
Angew.Chem.Int.Ed.Engl., 60:22776-22782, 2021

PubMed Abstract: Although β-hairpins are widespread in proteins, there is no tool to coax any small peptide to adopt a β-hairpin conformation, regardless of sequence. Here, we report that δ-linked γ(R)-methyl-ornithine ( MeOrn) provides an improved β-turn template for inducing a β-hairpin conformation in peptides. We developed a synthesis of protected MeOrn as a building block suitable for use in Fmoc-based solid-phase peptide synthesis. The synthesis begins with l-leucine and affords gram quantities of the N -Boc-N -Fmoc-γ(R)-methyl-ornithine building block. X-ray crystallography confirms that the MeOrn turn unit adopts a folded structure in a macrocyclic β-hairpin peptide. CD and NMR spectroscopy allow comparison of the MeOrn turn template to the δ-linked ornithine ( Orn) turn template that we previously introduced and to the popular d-Pro-Gly turn template. These studies show that the folding of the MeOrn turn template is substantially better than that of Orn and is comparable to d-Pro-Gly.

PubMed: 34258835
DOI: 10.1002/anie.202105559

Experimental method

X-RAY DIFFRACTION (1.1 Å)