Identification of a small molecule [beta]-secretase inhibitor that binds without catalytic aspartate engagement

Journal Article · Thu Sep 02 00:00:00 EDT 2010 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmcl.2008.11.027· OSTI ID:1005678

Steele, Thomas G; Hills, Ivory D; Nomland, Ashley A; de León, Pablo; Allison, Timothy; McGaughey, Georgia; Colussi, Dennis; Tugusheva, Katherine; Haugabook, Sharie J; Espeseth, Amy S; Zuck, Paul; Graham, Samuel L; Stachel, Shawn J

A small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding. This unprecedented binding mode in the field of aspartyl protease inhibition is described.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005678
• Journal Information: Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (1) ; 01, 2009 Vol. 19; ISSN 0960-894X
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
CRYSTALLOGRAPHY
ENZYMES
INHIBITION
MOLECULES
RESIDUES