2IRZ

Crystal structure of human Beta-secretase complexed with inhibitor

Summary for 2IRZ

• Entry DOI: 10.2210/pdb2irz/pdb
• Related: 1TQF 2B8V 2IS0
• Descriptor: Beta-secretase 1, 3-{5-[(1R)-1-AMINO-1-METHYL-2-PHENYLETHYL]-1,3,4-OXADIAZOL-2-YL}-N-[(1R)-1-(4-FLUOROPHENYL)ETHYL]-5-[METHYL(METHYLSULFONYL)AMINO]BENZAMIDE (3 entities in total)
• Functional Keywords: aspartyl protease, 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: 45674.38

Authors

Munshi, S. (deposition date: 2006-10-16, release date: 2006-11-14, Last modification date: 2024-10-16)

Primary citation

Rajapakse, H.A.,Nantermet, P.G.,Selnick, H.G.,Munshi, S.,McGaughey, G.B.,Lindsley, S.R.,Young, M.B.,Lai, M.T.,Espeseth, A.S.,Shi, X.P.,Colussi, D.,Pietrak, B.,Crouthamel, M.C.,Tugusheva, K.,Huang, Q.,Xu, M.,Simon, A.J.,Kuo, L.,Hazuda, D.J.,Graham, S.,Vacca, J.P.
Discovery of oxadiazoyl tertiary carbinamine inhibitors of beta-secretase (BACE-1).
J.Med.Chem., 49:7270-7273, 2006

PubMed Abstract: We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere derived inhibitors of BACE-1.

PubMed: 17149856
DOI: 10.1021/jm061046r

Experimental method

X-RAY DIFFRACTION (1.8 Å)