8A19

Structure of a leucinostatin derivative determined by host lattice display : L1E4V1 construct

Summary for 8A19

• Entry DOI: 10.2210/pdb8a19/pdb
• Descriptor: L1E4v1, 6-(2-methoxyethoxy)-11,15-dimethyl-8-oxa-2,11,15,19,21,23-hexazatetracyclo[15.6.1.13,7.020,24]pentacosa-1(23),3(25),4,6,17,20(24),21-heptaen-10-one, MANGANESE (II) ION, ... (7 entities in total)
• Functional Keywords: host lattice display, leucinostatin, engbf, darpin, de novo protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 149230.08

Authors

Mittl, P.R.E. (deposition date: 2022-06-01, release date: 2022-12-07, Last modification date: 2024-01-31)

Primary citation

Kiss, C.,Gall, F.M.,Dreier, B.,Adams, M.,Riedl, R.,Pluckthun, A.,Mittl, P.R.E.
Structure of a hydrophobic leucinostatin derivative determined by host lattice display.
Acta Crystallogr D Struct Biol, 78:1439-1450, 2022

PubMed 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.

PubMed: 36458615
DOI: 10.1107/S2059798322010762

Experimental method

X-RAY DIFFRACTION (2.358 Å)