De novo design of a hyperstable non-natural protein-ligand complex with sub-Å accuracy.
Published
Journal Article
Protein catalysis requires the atomic-level orchestration of side chains, substrates and cofactors, and yet the ability to design a small-molecule-binding protein entirely from first principles with a precisely predetermined structure has not been demonstrated. Here we report the design of a novel protein, PS1, that binds a highly electron-deficient non-natural porphyrin at temperatures up to 100 °C. The high-resolution structure of holo-PS1 is in sub-Å agreement with the design. The structure of apo-PS1 retains the remote core packing of the holoprotein, with a flexible binding region that is predisposed to ligand binding with the desired geometry. Our results illustrate the unification of core packing and binding-site definition as a central principle of ligand-binding protein design.
Full Text
Duke Authors
Cited Authors
- Polizzi, NF; Wu, Y; Lemmin, T; Maxwell, AM; Zhang, S-Q; Rawson, J; Beratan, DN; Therien, MJ; DeGrado, WF
Published Date
- December 2017
Published In
Volume / Issue
- 9 / 12
Start / End Page
- 1157 - 1164
PubMed ID
- 29168496
Pubmed Central ID
- 29168496
Electronic International Standard Serial Number (EISSN)
- 1755-4349
International Standard Serial Number (ISSN)
- 1755-4330
Digital Object Identifier (DOI)
- 10.1038/nchem.2846
Language
- eng