6N9H

De novo designed homo-trimeric amantadine-binding protein

Summary for 6N9H

• Entry DOI: 10.2210/pdb6n9h/pdb
• Descriptor: amantadine-binding protein, (3S,5S,7S)-tricyclo[3.3.1.1~3,7~]decan-1-amine, SODIUM ION, ... (4 entities in total)
• Functional Keywords: helical bundle, trimer, amantadine-binding protein, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 9313.75

Authors

Park, J.,Baker, D. (deposition date: 2018-12-03, release date: 2019-12-18, Last modification date: 2024-04-03)

Primary citation

Park, J.,Selvaraj, B.,McShan, A.C.,Boyken, S.E.,Wei, K.Y.,Oberdorfer, G.,DeGrado, W.,Sgourakis, N.G.,Cuneo, M.J.,Myles, D.A.,Baker, D.
De novo design of a homo-trimeric amantadine-binding protein.
Elife, 8:-, 2019

PubMed Abstract: The computational design of a symmetric protein homo-oligomer that binds a symmetry-matched small molecule larger than a metal ion has not yet been achieved. We used de novo protein design to create a homo-trimeric protein that binds the C symmetric small molecule drug amantadine with each protein monomer making identical interactions with each face of the small molecule. Solution NMR data show that the protein has regular three-fold symmetry and undergoes localized structural changes upon ligand binding. A high-resolution X-ray structure reveals a close overall match to the design model with the exception of water molecules in the amantadine binding site not included in the Rosetta design calculations, and a neutron structure provides experimental validation of the computationally designed hydrogen-bond networks. Exploration of approaches to generate a small molecule inducible homo-trimerization system based on the design highlight challenges that must be overcome to computationally design such systems.

PubMed: 31854299
DOI: 10.7554/eLife.47839

Experimental method

X-RAY DIFFRACTION (1.039 Å)