2a3x
From Proteopedia
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'''Decameric crystal structure of human serum amyloid P-component bound to Bis-1,2-{[(Z)-2carboxy- 2-methyl-1,3-dioxane]- 5-yloxycarbonyl}-piperazine''' | '''Decameric crystal structure of human serum amyloid P-component bound to Bis-1,2-{[(Z)-2carboxy- 2-methyl-1,3-dioxane]- 5-yloxycarbonyl}-piperazine''' | ||
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[[Category: Paszkiewicz, E.]] | [[Category: Paszkiewicz, E.]] | ||
[[Category: Sadowska, J.]] | [[Category: Sadowska, J.]] | ||
| - | [[Category: | + | [[Category: Multivalent ligand]] |
| - | [[Category: | + | [[Category: Serum amyloid]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:34:13 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 15:34, 3 May 2008
Decameric crystal structure of human serum amyloid P-component bound to Bis-1,2-{[(Z)-2carboxy- 2-methyl-1,3-dioxane]- 5-yloxycarbonyl}-piperazine
Overview
A comprehensive series of solution and crystallographic studies reveal how simple, achiral, bivalent ligands of the cyclic pyruvate of glycerol promote face-to-face complex formation of the pentraxin, serum amyloid P component (SAP) into decamers. SAP, a protein of the human innate immune system, is universally present in amyloids, including cerebral amyloid deposits found in the brain of Alzheimer disease patients. Removal of SAP through a specific aggregation mechanism mediated by multivalent ligands appears to provide therapeutic benefit in the progression of this disease. Crystallographic studies reveal that in our novel series of ligands only the methyl and carboxylate moieties of the pyruvate ketal directly interact with the protein, but the geometric constraints imposed by the tether dictate which of two chair conformations are adopted by the pyruvate dioxane ring. Solution studies, as interpreted through a simple thermodynamic model, account for the distribution of pentameric and decameric bound states at different ligand concentrations and indicate that differences in the flexibility of the tether determine the geometry and stability of the specific aggregates formed between SAP and two different bivalent ligands. The factors affecting the design of ligands promoting face-to-face protein dimerization as well as potential biological implications are discussed.
About this Structure
2A3X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Ligand-assisted aggregation of proteins. Dimerization of serum amyloid P component by bivalent ligands., Ho JG, Kitov PI, Paszkiewicz E, Sadowska J, Bundle DR, Ng KK, J Biol Chem. 2005 Sep 9;280(36):31999-2008. Epub 2005 Jul 20. PMID:16036920 Page seeded by OCA on Sat May 3 18:34:13 2008
