8R02

Crystal structure of the retromer complex VPS29/VPS35 with the ligand bis-1,3-phenyl guanylhydrazone, 2a

Summary for 8R02

• Entry DOI: 10.2210/pdb8r02/pdb
• Descriptor: Vacuolar protein sorting-associated protein 29, Vacuolar protein sorting-associated protein 35, Bis-1,3-phenyl guanylhydrazon, ... (4 entities in total)
• Functional Keywords: complex, transport, recycling, ligand, protein transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 112592.76

Authors

Milani, M.,Fagnani, E. (deposition date: 2023-10-30, release date: 2024-03-27)

Primary citation

Fagnani, E.,Boni, F.,Seneci, P.,Gornati, D.,Muzio, L.,Mastrangelo, E.,Milani, M.
Stabilization of the retromer complex: Analysis of novel binding sites of bis-1,3-phenyl guanylhydrazone 2a to the VPS29/VPS35 interface.
Comput Struct Biotechnol J, 23:1088-1093, 2024

PubMed Abstract: The stabilization of the retromer protein complex can be effective in the treatment of different neurological disorders. Following the identification of bis-1,3-phenyl guanylhydrazone as an effective new compound for the treatment of amyotrophic lateral sclerosis, in this work we analyze the possible binding sites of this molecule to the VPS35/VPS29 dimer of the retromer complex. Our results show that the affinity for different sites of the protein assembly depends on compound charge and therefore slight changes in the cell microenvironment could promote different binding states. Finally, we describe a novel binding site located in a deep cleft between VPS29 and VPS35 that should be further explored to select novel molecular chaperones for the stabilization of the retromer complex.

PubMed: 38487369
DOI: 10.1016/j.csbj.2024.02.026

Experimental method

X-RAY DIFFRACTION (2.5 Å)