2ot1
Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with naphthol AS-E phosphate, a competitive inhibitor
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OverviewOverview
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.
About this StructureAbout this Structure
2OT1 is a Single protein structure of sequence from Oryctolagus cuniculus with as ligand. Active as Fructose-bisphosphate aldolase, with EC number 4.1.2.13 Full crystallographic information is available from OCA.
ReferenceReference
A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein., St-Jean M, Izard T, Sygusch J, J Biol Chem. 2007 May 11;282(19):14309-15. Epub 2007 Feb 27. PMID:17329259
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