De novo design of a hyperstable non-natural protein-ligand complex with sub-Å accuracy.
Nat Chem
; 9(12): 1157-1164, 2017 12.
Article
in En
| MEDLINE
| ID: mdl-29168496
ABSTRACT
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:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Porphyrins
/
Proteins
Language:
En
Journal:
Nat Chem
Year:
2017
Document type:
Article