2qge
From Proteopedia
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|PDB= 2qge |SIZE=350|CAPTION= <scene name='initialview01'>2qge</scene>, resolution 1.450Å | |PDB= 2qge |SIZE=350|CAPTION= <scene name='initialview01'>2qge</scene>, resolution 1.450Å | ||
|SITE= <scene name='pdbsite=AC1:Mr6+Binding+Site+For+Residue+B+200'>AC1</scene> and <scene name='pdbsite=AC2:Mr6+Binding+Site+For+Residue+A+201'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:Mr6+Binding+Site+For+Residue+B+200'>AC1</scene> and <scene name='pdbsite=AC2:Mr6+Binding+Site+For+Residue+A+201'>AC2</scene> | ||
| - | |LIGAND= <scene name='pdbligand=MR6:'>MR6</scene> | + | |LIGAND= <scene name='pdbligand=MR6:2-(3,5-DIMETHYLPHENYL)-1,3-BENZOXAZOLE'>MR6</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qge OCA], [http://www.ebi.ac.uk/pdbsum/2qge PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qge RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Connelly, S.]] | [[Category: Connelly, S.]] | ||
| - | [[Category: MR6]] | ||
[[Category: amyloidogenesis inhibitor]] | [[Category: amyloidogenesis inhibitor]] | ||
[[Category: hormone/growth factor complex]] | [[Category: hormone/growth factor complex]] | ||
| Line 29: | Line 31: | ||
[[Category: transthyretin]] | [[Category: transthyretin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:49:00 2008'' |
Revision as of 01:49, 31 March 2008
| |||||||
| , resolution 1.450Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | TTR, PALB (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human transthyretin (TTR) complexed with 2-(3,5-Dimethylphenyl)benzoxazole
Overview
To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 A) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.
About this Structure
2QGE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based transthyretin amyloidogenesis inhibitors., Johnson SM, Connelly S, Wilson IA, Kelly JW, J Med Chem. 2008 Jan 24;51(2):260-70. Epub 2007 Dec 21. PMID:18095641
Page seeded by OCA on Mon Mar 31 04:49:00 2008
