2Q11

Structure of BACE complexed to compound 1

Summary for 2Q11

• Entry DOI: 10.2210/pdb2q11/pdb
• Descriptor: Beta-secretase 1, 3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL)-N-CYCLOHEXYL-N-METHYLPROPANAMIDE (3 entities in total)
• Functional Keywords: bace inhibitor complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 131191.17

Authors

Sharff, A.J. (deposition date: 2007-05-23, release date: 2007-08-14, Last modification date: 2024-11-06)

Primary citation

Baxter, E.W.,Conway, K.A.,Kennis, L.,Bischoff, F.,Mercken, M.H.,Winter, H.L.,Reynolds, C.H.,Tounge, B.A.,Luo, C.,Scott, M.K.,Huang, Y.,Braeken, M.,Pieters, S.M.,Berthelot, D.J.,Masure, S.,Bruinzeel, W.D.,Jordan, A.D.,Parker, M.H.,Boyd, R.E.,Qu, J.,Alexander, R.S.,Brenneman, D.E.,Reitz, A.B.
2-Amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (beta-Site APP cleaving enzyme): Use of structure based design to convert a micromolar hit into a nanomolar lead.
J.Med.Chem., 50:4261-4264, 2007

PubMed Abstract: A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 microM to 11 nM K(i)) by substitution into the unoccupied S(1)' pocket.

PubMed: 17685503
DOI: 10.1021/jm0705408

Experimental method

X-RAY DIFFRACTION (2.4 Å)