3LHG

Bace1 in complex with the aminohydantoin Compound 4g

Summary for 3LHG

• Entry DOI: 10.2210/pdb3lhg/pdb
• Descriptor: Beta-secretase 1, (5S)-2-amino-5-(2',5'-difluorobiphenyl-3-yl)-3-methyl-5-pyridin-4-yl-3,5-dihydro-4H-imidazol-4-one (3 entities in total)
• Functional Keywords: inhibitor, aminohydantoin, 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: 46819.36

Authors

Olland, A.M. (deposition date: 2010-01-22, release date: 2010-04-21, Last modification date: 2024-10-09)

Primary citation

Zhou, P.,Li, Y.,Fan, Y.,Wang, Z.,Chopra, R.,Olland, A.,Hu, Y.,Magolda, R.L.,Pangalos, M.,Reinhart, P.H.,Turner, M.J.,Bard, J.,Malamas, M.S.,Robichaud, A.J.
Pyridinyl aminohydantoins as small molecule BACE1 inhibitors.
Bioorg.Med.Chem.Lett., 20:2326-2329, 2010

PubMed Abstract: A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC(50) of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2' region of the enzyme that contributed to increased potency.

PubMed: 20202842
DOI: 10.1016/j.bmcl.2010.01.136

Experimental method

X-RAY DIFFRACTION (2.1 Å)