5TOL

CRYSTAL STRUCTURE OF BETA-SITE APP-CLEAVING ENZYME 1 COMPLEXED WITH N-(3-((4AS,7AS)-2-AMINO-4,4A,5,6-TETRAHYDRO-7AH-FURO[2,3-D][1,3]THIAZIN-7A-YL)-4-FLUOROPHENYL)-5-BROMO-2-PYRIDINECARBOXAMIDE

Summary for 5TOL

• Entry DOI: 10.2210/pdb5tol/pdb
• Descriptor: Beta-secretase 1, N-{3-[(4aR,7aR)-2-amino-4,4a,5,6-tetrahydro-7aH-furo[2,3-d][1,3]thiazin-7a-yl]-4-fluorophenyl}-5-bromopyridine-2-carboxamide (3 entities in total)
• Functional Keywords: aspartyl protease, bace1, kiaa1149, asp2, flj90568, bace, hspc104, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 46374.86

Authors

Muckelbauer, J.K. (deposition date: 2016-10-18, release date: 2016-11-23, Last modification date: 2024-11-06)

Primary citation

Wu, Y.J.,Guernon, J.,Rajamani, R.,Toyn, J.H.,Ahlijanian, M.K.,Albright, C.F.,Muckelbauer, J.,Chang, C.,Camac, D.,Macor, J.E.,Thompson, L.A.
Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.
Bioorg.Med.Chem.Lett., 26:5729-5731, 2016

PubMed Abstract: This Letter describes the synthesis and structure-activity relationships of a series of furo[2,3-d][1,3]thiazinamine BACE1 inhibitors. The co-crystal structure of a representative thiazinamine 2e bound with the BACE1 active site displayed a binding mode driven by interactions with the catalytic aspartate dyad and engagement of the biaryl amide toward the S1 and S3 pockets. This work indicates that furo[2,3-d]thiazine can serve as a viable bioisostere of the known furo[3,4-d]thiazine.

PubMed: 27816517
DOI: 10.1016/j.bmcl.2016.10.055

Experimental method

X-RAY DIFFRACTION (2.51 Å)