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Publication Abstract from PubMed

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 degrees C. The high-resolution structure of holo-PS1 is in sub-A 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.

De novo design of a hyperstable non-natural protein-ligand complex with sub-A accuracy.,Polizzi NF, Wu Y, Lemmin T, Maxwell AM, Zhang SQ, Rawson J, Beratan DN, Therien MJ, DeGrado WF Nat Chem. 2017 Dec;9(12):1157-1164. doi: 10.1038/nchem.2846. Epub 2017 Aug 21. PMID:29168496^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.