9DM3

De novo design of proteins that bind naphthalenediimides, powerful photooxidants with tunable photophysical properties

Summary for 9DM3

• Entry DOI: 10.2210/pdb9dm3/pdb
• NMR Information: BMRB: 52600
• Descriptor: naphthalenediimide binding protein (1 entity in total)
• Functional Keywords: naphthalenediimides, photophysical properties, de novo protein
• Biological source: Helicana
• Total number of polymer chains: 1
• Total formula weight: 15199.81

Authors

Wu, Y.,Mann, S.I.,DeGrado, W.F. (deposition date: 2024-09-12, release date: 2025-03-05, Last modification date: 2025-03-19)

Primary citation

Mann, S.I.,Lin, Z.,Tan, S.K.,Zhu, J.,Widel, Z.X.W.,Bakanas, I.,Mansergh, J.P.,Liu, R.,Kelly, M.J.S.,Wu, Y.,Wells, J.A.,Therien, M.J.,DeGrado, W.F.
De Novo Design of Proteins That Bind Naphthalenediimides, Powerful Photooxidants with Tunable Photophysical Properties.
J.Am.Chem.Soc., 147:7849-7858, 2025

PubMed Abstract: protein design provides a framework to test our understanding of protein function and build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidants and the evaluation of the use of these proteins to generate diffusible small-molecule reactive species. Because excited-state dynamics are influenced by the dynamics and hydration of a photooxidant's environment, it was important to not only design a binding site but also to evaluate its dynamic properties. Thus, we used computational design in conjunction with molecular dynamics (MD) simulations to design a protein, designated NBP (DI inding rotein), that held a naphthalenediimide (NDI), a powerful photooxidant, in a programmable molecular environment. Solution NMR confirmed the structure of the complex. We evaluated two NDI cofactors in this protein using ultrafast pump-probe spectroscopy to evaluate light-triggered intra- and intermolecular electron transfer function. Moreover, we demonstrated the utility of this platform to activate multiple molecular probes for protein labeling.

PubMed: 39982408
DOI: 10.1021/jacs.4c18151

Experimental method

SOLUTION NMR