2OT0

Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein

Summary for 2OT0

• Entry DOI: 10.2210/pdb2ot0/pdb
• Related: 2OT1
• Descriptor: Fructose-bisphosphate aldolase A, Wiskott-Aldrich syndrome protein C-terminal peptide (3 entities in total)
• Functional Keywords: complex, glycolysis, actin dynamics, hydrophobic pocket, wasp, lyase
• Biological source: Oryctolagus cuniculus (rabbit); More
• Cellular location: Cytoplasm, cytoskeleton: P42768
• Total number of polymer chains: 8
• Total formula weight: 164184.90

Authors

St-Jean, M.,Izard, T.,Sygusch, J. (deposition date: 2007-02-07, release date: 2007-02-27, Last modification date: 2023-08-30)

Primary citation

St-Jean, M.,Izard, T.,Sygusch, J.
A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with wiskott-Aldrich syndrome protein.
J.Biol.Chem., 282:14309-14315, 2007

PubMed Abstract: Aldolase plays essential catalytic roles in glycolysis and gluconeogenesis. However, aldolase is a highly abundant protein that is remarkably promiscuous in its interactions with other cellular proteins. In particular, aldolase binds to highly acidic amino acid sequences, including the C terminus of the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor. Here we report the crystal structure of tetrameric rabbit muscle aldolase in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein. Aldolase recognizes a short, four-residue DEWD motif (residues 498-501), which adopts a loose hairpin turn that folds around the central aromatic residue, enabling its tryptophan side chain to fit into a hydrophobic pocket in the active site of aldolase. The flanking acidic residues in this binding motif provide further interactions with conserved aldolase active site residues Arg-42 and Arg-303, aligning their side chains and forming the sides of the hydrophobic pocket. The binding of Wiskott-Aldrich syndrome protein to aldolase precludes intramolecular interactions of its C terminus with its active site and is competitive with substrate as well as with binding by actin and cortactin. Finally, based on this structure, a novel naphthol phosphate-based inhibitor of aldolase was identified, and its structure in complex with aldolase demonstrated mimicry of the Wiskott-Aldrich syndrome protein-aldolase interaction. The data support a model whereby aldolase exists in distinct forms that regulate glycolysis or actin dynamics.

PubMed: 17329259
DOI: 10.1074/jbc.M611505200

Experimental method

X-RAY DIFFRACTION (2.05 Å)