5KWO

NMR Solution Structure of Designed Peptide NC_EHE_D1

5KWO の概要

• エントリーDOI: 10.2210/pdb5kwo/pdb
• 関連するPDBエントリー: 5KVN 5KWP 5KWX 5KWZ 5KX0 5KX1 5KX2
• NMR情報: BMRB: 30140
• 分子名称: Designed peptide NC_EHE_D1 (1 entity in total)
• 機能のキーワード: designed peptide, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3302.74

構造登録者

Harvey, P.J.,Craik, D.J. (登録日: 2016-07-18, 公開日: 2016-09-21, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

SOLUTION NMR