2ot0
From Proteopedia
(New page: 200px<br /> <applet load="2ot0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ot0, resolution 2.05Å" /> '''Fructose-1,6-bispho...) |
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caption="2ot0, resolution 2.05Å" /> | caption="2ot0, resolution 2.05Å" /> | ||
'''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein'''<br /> | '''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein'''<br /> | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Neutropenia, severe congenital, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Thrombocytopenia, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Thrombocytopenia, X-linked, intermittent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Wiskott-Aldrich syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2OT0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Active as [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] Full crystallographic information is available from [http:// | + | 2OT0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OT0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: wasp]] | [[Category: wasp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:04:49 2008'' |
Revision as of 13:04, 23 January 2008
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Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein
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
2OT0 is a Protein complex structure of sequences from Oryctolagus cuniculus. Active as Fructose-bisphosphate aldolase, with EC number 4.1.2.13 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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