1dvy: Difference between revisions
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|PDB= 1dvy |SIZE=350|CAPTION= <scene name='initialview01'>1dvy</scene>, resolution 1.9Å | |PDB= 1dvy |SIZE=350|CAPTION= <scene name='initialview01'>1dvy</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=BPD:N-(M-TRIFLUOROMETHYLPHENYL) PHENOXAZINE-4,6-DICARBOXYLIC ACID'>BPD</scene> | |LIGAND= <scene name='pdbligand=BPD:N-(M-TRIFLUOROMETHYLPHENYL)+PHENOXAZINE-4,6-DICARBOXYLIC+ACID'>BPD</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1bmz|1BMZ]], [[1dvq|1DVQ]], [[1dvs|1DVS]], [[1dvt|1DVT]], [[1dvu|1DVU]], [[1dvx|1DVX]], [[1dvz|1DVZ]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dvy OCA], [http://www.ebi.ac.uk/pdbsum/1dvy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dvy RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases. | The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Petrassi, H M.]] | [[Category: Petrassi, H M.]] | ||
[[Category: Sacchettini, J C.]] | [[Category: Sacchettini, J C.]] | ||
[[Category: signaling protein]] | [[Category: signaling protein]] | ||
[[Category: thyroxine transport]] | [[Category: thyroxine transport]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:49:50 2008'' | ||
Revision as of 19:49, 30 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Related: | 1BMZ, 1DVQ, 1DVS, 1DVT, 1DVU, 1DVX, 1DVZ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF TRANSTHYRETIN IN COMPLEX WITH N-(M-TRIFLUOROMETHYLPHENYL) PHENOXAZINE-4,6-DICARBOXYLIC ACID
OverviewOverview
The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases.
About this StructureAbout this Structure
1DVY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Rational design of potent human transthyretin amyloid disease inhibitors., Klabunde T, Petrassi HM, Oza VB, Raman P, Kelly JW, Sacchettini JC, Nat Struct Biol. 2000 Apr;7(4):312-21. PMID:10742177
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