1bm7
From Proteopedia
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| , resolution 2.00Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN TRANSTHYRETIN (PREALBUMIN) COMPLEX WITH FLUFENAMIC ACID (2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID)
Overview
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.
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
Page seeded by OCA on Sun Mar 30 19:03:54 2008
