2oah
Crystal Structure of Human Beta Secretase Complexed with inhibitor
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| , resolution 1.80Å | |||||||
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| Ligands: | |||||||
| Gene: | BACE1, BACE (Homo sapiens) | ||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.
About this StructureAbout this Structure
2OAH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation., Stauffer SR, Stanton MG, Gregro AR, Steinbeiser MA, Shaffer JR, Nantermet PG, Barrow JC, Rittle KE, Collusi D, Espeseth AS, Lai MT, Pietrak BL, Holloway MK, McGaughey GB, Munshi SK, Hochman JH, Simon AJ, Selnick HG, Graham SL, Vacca JP, Bioorg Med Chem Lett. 2007 Mar 15;17(6):1788-92. Epub 2006 Dec 21. PMID:17257835
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