5JG9

Crystal structure of the de novo mini protein gEHEE_06

Summary for 5JG9

• Entry DOI: 10.2210/pdb5jg9/pdb
• Descriptor: de novo design, hyper stable, disulfide-rich mini protein, CHLORIDE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: de novo design of hyper stable, disulfide-rich, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 3
• Total formula weight: 17658.24

Authors

Rupert, P.B.,Johnsen, W.A. (deposition date: 2016-04-19, release date: 2016-09-28, Last modification date: 2024-11-06)

Primary citation

Bhardwaj, G.,Mulligan, V.K.,Bahl, C.D.,Gilmore, J.M.,Harvey, P.J.,Cheneval, O.,Buchko, G.W.,Pulavarti, S.V.,Kaas, Q.,Eletsky, A.,Huang, P.S.,Johnsen, W.A.,Greisen, P.J.,Rocklin, G.J.,Song, Y.,Linsky, T.W.,Watkins, A.,Rettie, S.A.,Xu, X.,Carter, L.P.,Bonneau, R.,Olson, J.M.,Coutsias, E.,Correnti, C.E.,Szyperski, T.,Craik, D.J.,Baker, D.
Accurate de novo design of hyperstable constrained peptides.
Nature, 538:329-335, 2016

PubMed Abstract: Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18-47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N-C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.

PubMed: 27626386
DOI: 10.1038/nature19791

Experimental method

X-RAY DIFFRACTION (2.09 Å)