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1f64
From Proteopedia
(Difference between revisions)
(New page: '''Theoretical Model''' The entry 1F64 is a Theoretical Model titled 'LEU55PRO TTR-IDOX THEORETICAL MODEL'. Category:Theoretical Model ''Page seeded by [http://oca.weizmann.ac.il/o...) |
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| - | + | {{Theoretical_model}} | |
| - | + | ==LEU55PRO TTR-IDOX THEORETICAL MODEL== | |
| + | <StructureSection load='1f64' size='340' side='right'caption='[[1f64]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F64 FirstGlance]. <br> | ||
| + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1f64 FirstGlance], [https://www.ebi.ac.uk/pdbsum/1f64 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f64 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The crystal structure of the amyloidogenic Leu-55Pro transthyretin (TTR) variant has revealed an oligomer structure that may represent a putative amyloid protofibril [Sebastiao, Saraiva and Damas (1998) J. Biol. Chem. 273, 24715-24722]. Here we report biochemical evidence that corroborates the isolation of an intermediate structure, an 'amyloid-like' oligomer, which is most probably present in the biochemical pathway that leads to amyloid deposition and that was isolated by the crystallization of the Leu-55Pro TTR variant. 4'-Iodo-4'-deoxydoxorubicin (IDOX) is a compound that interacts with amyloid fibrils of various compositions and it has been reported to reduce the amyloid load in immunoglobulin light chain amyloidosis [Merlini, Ascari, Amboldi, Bellotti, Arbustini, Perfetti, Ferrari, Zorzoli, Marinone, Garini et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 2959-2963]. In this work, we observed that the monoclinic Leu-55Pro TTR crystals, soaked with IDOX, undergo rapid dissociation. Moreover, under the same conditions, the orthorhombic wild-type TTR crystals are quite stable. This is explained by the different TTR conformations isolated upon crystallization of the two proteins; while the Leu-55Pro TTR exhibits the necessary conformation for IDOX binding, the same structure is not present in the crystallized wild-type protein. A theoretical model concerning the interaction of Leu-55Pro TTR with IDOX, which is consistent with the dissociation of the amyloid-like oligomer, is presented. In this model the IDOX iodine atom is buried in a pocket located between the two beta-sheets of the Leu-55Pro TTR monomer with the IDOX aromatic-moiety long axis nearly perpendicular to the direction of the beta-sheets. | ||
| - | + | The molecular interaction of 4'-iodo-4'-deoxydoxorubicin with Leu-55Pro transthyretin 'amyloid-like' oligomer leading to disaggregation.,Sebastiao MP, Merlini G, Saraiva MJ, Damas AM Biochem J. 2000 Oct 1;351(Pt 1):273-9. PMID:10998371<ref>PMID:10998371</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 1f64" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Theoretical Model]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Sebastiao, M P]] | ||
Current revision
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LEU55PRO TTR-IDOX THEORETICAL MODEL
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