Engineering a zinc binding site into the de novo designed protein DS119 with a βαβ structure

Abstract

Functional proteins designed de novo have potential application in chemical engineering, agriculture and healthcare. Metal binding sites are commonly used to incorporate functions. Based on a de novo designed protein DS119 with a βαβ structure, we have computationally engineered zinc binding sites into it using a home-made searching program. Seven out of the eight designed sequences tested were shown to bind Zn²⁺ with micromolar affinity, and one of them bound Zn²⁺ with 1:1 stoichiometry. This is the first time that metalloproteins with an α, β mixed structure have been designed from scratch.

Keywords

βαβ / de novo / design / folding / zinc- binding