Engineering a zinc binding site into the de novo designed protein DS119 with a βαβ structure.
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 Zn(2+) with micromolar affinity, and one of them bound Zn(2+) with 1:1 stoichiometry. This is the first time that metalloproteins with an α, β mixed structure have been designed from scratch.
Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Cheng
C
Zhu
Changsheng
C
Zhang
Huanhuan
H
Liang
Luhua
L
Lai
D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D004926:Escherichia coli; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
D008667:Metalloproteins; D011994:Recombinant Proteins; D015032:Zinc