9DBV

Cu-Bound Structure of Computationally Designed Homotetramer PW1

Summary for 9DBV

• Entry DOI: 10.2210/pdb9dbv/pdb
• Descriptor: Computationally Designed PW1, COPPER (II) ION (3 entities in total)
• Functional Keywords: metalloprotein, computational design, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 12040.66

Authors

Hoffnagle, A.M.,Tezcan, F.A. (deposition date: 2024-08-23, release date: 2025-08-27, Last modification date: 2026-03-11)

Primary citation

Hoffnagle, A.M.,Herold, R.A.,Tsai, C.Y.,Shiau, A.A.,Britt, R.D.,Tezcan, F.A.
De Novo Design of a Metalloprotein with a Synthetically Inspired Dinuclear Paddlewheel Coordination Motif.
J.Am.Chem.Soc., 147:40788-40798, 2025

PubMed Abstract: A metal-centered design approach was used to design a tetrameric protein assembly, PW1, with a new-to-nature metal center inspired by the structures of transition metal paddlewheel complexes such as di-Cu tetraacetate. The structure of PW1 matches the design prediction with atomic accuracy, preorganizing four Glu residues to form the desired dinuclear Cu center. Notably, Cu-PW1 has a reduction potential of -0.085 V at pH 7.0, which is more negative than any natural or engineered Cu redox protein. In addition to Cu, PW1 can also scaffold Rh ions in the dinuclear paddlewheel geometry as well as trivalent lanthanide ions in a mononuclear fashion. These results demonstrate the feasibility of designing new protein architectures around synthetically inspired, nonbiological metal centers, thus expanding the scope of artificial metalloproteins beyond those constructed around pre-existing protein scaffolds and opening new avenues to discover structure-function relationships outside the constraints of natural evolution.

PubMed: 41143657
DOI: 10.1021/jacs.5c13813

Experimental method

X-RAY DIFFRACTION (1.8 Å)