1bm7

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{{STRUCTURE_1bm7| PDB=1bm7 | SCENE= }}
{{STRUCTURE_1bm7| PDB=1bm7 | SCENE= }}
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'''HUMAN TRANSTHYRETIN (PREALBUMIN) COMPLEX WITH FLUFENAMIC ACID (2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID)'''
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===HUMAN TRANSTHYRETIN (PREALBUMIN) COMPLEX WITH FLUFENAMIC ACID (2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID)===
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==Overview==
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Insoluble protein fibrils resulting from the self-assembly of a conformational intermediate are implicated as the causative agent in several severe human amyloid diseases, including Alzheimer's disease, familial amyloid polyneuropathy, and senile systemic amyloidosis. The latter two diseases are associated with transthyretin (TTR) amyloid fibrils, which appear to form in the acidic partial denaturing environment of the lysosome. Here we demonstrate that flufenamic acid (Flu) inhibits the conformational changes of TTR associated with amyloid fibril formation. The crystal structure of TTR complexed with Flu demonstrates that Flu mediates intersubunit hydrophobic interactions and intersubunit hydrogen bonds that stabilize the normal tetrameric fold of TTR. A small-molecule inhibitor that stabilizes the normal conformation of a protein is desirable as a possible approach to treat amyloid diseases. Molecules such as Flu also provide the means to rigorously test the amyloid hypothesis, i.e., the apparent causative role of amyloid fibrils in amyloid disease.
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{{ABSTRACT_PUBMED_9789022}}
==About this Structure==
==About this Structure==
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[[Category: Sacchettini, J C.]]
[[Category: Sacchettini, J C.]]
[[Category: Thyroxine transport]]
[[Category: Thyroxine transport]]
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Revision as of 16:22, 30 June 2008

Template:STRUCTURE 1bm7

HUMAN TRANSTHYRETIN (PREALBUMIN) COMPLEX WITH FLUFENAMIC ACID (2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID)

Template:ABSTRACT PUBMED 9789022

About this Structure

1BM7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Inhibiting transthyretin conformational changes that lead to amyloid fibril formation., Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchettini JC, Kelly JW, Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12956-60. PMID:9789022

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