View source for 2ot1

[[Image:2ot1.gif|left|200px]]

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{{STRUCTURE_2ot1|  PDB=2ot1  |  SCENE=  }} 

'''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with naphthol AS-E phosphate, a competitive inhibitor'''


==Overview==
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 Structure==
2OT1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OT1 OCA]. 

==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/17329259 17329259]
[[Category: Fructose-bisphosphate aldolase]]
[[Category: Oryctolagus cuniculus]]
[[Category: Single protein]]
[[Category: Izard, T.]]
[[Category: St-Jean, M.]]
[[Category: Sygusch, J.]]
[[Category: Competitive inhibition]]
[[Category: Glycolysis]]
[[Category: Hydrophobic pocket]]
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