title: X-ray crystallographic structure of an artificial beta-sheet dimer.
abstract: This paper describes the X-ray crystallographic structure of a designed cyclic beta-sheet peptide that forms a well-defined hydrogen-bonded dimer that mimics beta-sheet dimers formed by proteins. The 54-membered ring macrocyclic peptide (1a) contains molecular template and turn units that induce beta-sheet structure in a heptapeptide strand that forms the dimerization interface. The X-ray crystallographic structure reveals the structures of the two "Hao" amino acids that help template the beta-sheet structure and the two delta-linked ornithine turn units that link the Hao-containing template to the heptapeptide beta-strand. The Hao amino acids adopt a conformation that resembles a tripeptide in a beta-strand conformation, with one edge of the Hao unit presenting an alternating array of hydrogen-bond donor and acceptor groups in the same pattern as that of a tripeptide beta-strand. The delta-linked ornithines adopt a conformation that resembles a hydrogen-bonded beta-turn, in which the ornithine takes the place of the i+1 and i+2 residues. The dimers formed by macrocyclic beta-sheet 1a resemble the dimers of many proteins, such as defensin HNP-3, the lambda-Cro repressor, interleukin 8, and the ribonuclease H domain of HIV-1 reverse transcriptase. The dimers of 1a self-assemble in the solid state into a barrel-shaped trimer of dimers in which the three dimers are arranged in a triangular fashion. Molecular modeling in which one of the three dimers is removed and the remaining two dimers are aligned face-to-face provides a model of the dimers of dimers of closely related macrocyclic beta-sheet peptides that were observed in solution.
authors.affiliation: Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Khakshoor
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Lin
authors.forename: Tyler P
authors.initials: TP
authors.lastname: Korman
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Shiou-Chuan
authors.initials: SC
authors.lastname: Tsai
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
authors.forename: James S
authors.initials: JS
authors.lastname: Nowick
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D010455:Peptides; D011506:Proteins