Structure of a hydrophobic leucinostatin derivative determined by host lattice display. Issue 12 (29th November 2022)

• Record Type: Journal Article
• Authors: Kiss, Cedric; Gall, Flavio M.; Dreier, Birgit; Adams, Michael; Riedl, Rainer; Plückthun, Andreas; Mittl, Peer R. E.
• Is Part Of: Acta crystallographica. Volume 78:Issue 12(2022)
• Page Start: 1439
• Page End: 1450
• Publication Date: 2022-11-29
• Subjects: crystal engineering -- host lattice display -- leucinostatins; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798322010762
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Host lattice display facilitated the crystallographic analysis of a hydrophobic peptide under aqueous conditions. Abstract : Peptides comprising many hydrophobic amino acids are almost insoluble under physiological buffer conditions, which complicates their structural analysis. To investigate the three‐dimensional structure of the hydrophobic leucinostatin derivative ZHAWOC6027, the previously developed host lattice display technology was applied. Two designed ankyrin‐repeat proteins (DARPins) recognizing a biotinylated ZHAWOC6027 derivative were selected from a diverse library by ribosome display under aqueous buffer conditions. ZHAWOC6027 was immobilized by means of the DARPin in the host lattice and the structure of the complex was determined by X‐ray diffraction. ZHAWOC6027 adopts a distorted α‐helical conformation. Comparison with the structures of related compounds that have been determined in organic solvents reveals elevated flexibility of the termini, which might be functionally important.