2ot1: Difference between revisions
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[[Image:2ot1.gif|left|200px]] | [[Image:2ot1.gif|left|200px]] | ||
'''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with naphthol AS-E phosphate, a competitive inhibitor''' | {{Structure | ||
|PDB= 2ot1 |SIZE=350|CAPTION= <scene name='initialview01'>2ot1</scene>, resolution 2.05Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=N3P:N-(4-CHLOROPHENYL)-3-(PHOSPHONOOXY)NAPHTHALENE-2-CARBOXAMIDE'>N3P</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] | |||
|GENE= ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |||
}} | |||
'''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with naphthol AS-E phosphate, a competitive inhibitor''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2OT1 is a [ | 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== | ==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:// | 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: Fructose-bisphosphate aldolase]] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
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[[Category: hydrophobic pocket]] | [[Category: hydrophobic pocket]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:04:04 2008'' | ||
Revision as of 16:04, 20 March 2008
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| 2ot1, resolution 2.05Å | |||||||||||||
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| Ligands: | N3P | ||||||||||||
| Gene: | ALDOA (Oryctolagus cuniculus) | ||||||||||||
| Activity: | Fructose-bisphosphate aldolase, with EC number 4.1.2.13 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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 Oryctolagus cuniculus. Full crystallographic information is available from 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:17329259
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