2PH6

Crystal Structure of Human Beta Secretase Complexed with inhibitor

Summary for 2PH6

• Entry DOI: 10.2210/pdb2ph6/pdb
• Related: 1TQF
• Descriptor: Beta-secretase 1, SULFATE ION, 3-({[(1R)-1-(4-FLUOROPHENYL)ETHYL]AMINO}CARBONYL)-5-[METHYL(METHYLSULFONYL)AMINO]BENZYL ALPHA-METHYL-D-PHENYLALANINATE, ... (4 entities in total)
• Functional Keywords: aspartyl protease, bace, 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: 45760.45

Authors

Munshi, S. (deposition date: 2007-04-10, release date: 2007-06-05, Last modification date: 2024-10-30)

Primary citation

Lindsley, S.R.,Moore, K.P.,Rajapakse, H.A.,Selnick, H.G.,Young, M.B.,Zhu, H.,Munshi, S.,Kuo, L.,McGaughey, G.B.,Colussi, D.,Crouthamel, M.C.,Lai, M.T.,Pietrak, B.,Price, E.A.,Sankaranarayanan, S.,Simon, A.J.,Seabrook, G.R.,Hazuda, D.J.,Pudvah, N.T.,Hochman, J.H.,Graham, S.L.,Vacca, J.P.,Nantermet, P.G.
Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Bioorg.Med.Chem.Lett., 17:4057-4061, 2007

PubMed Abstract: This Letter describes the design and synthesis of tertiary carbinamine macrocyclic inhibitors of the beta-secretase (BACE-1) enzyme. These macrocyclic inhibitors, some of which incorporate novel P2 substituents, display a 2- to 100-fold increase in potency relative to the previously described acyclic analogs while affording greater stability.

PubMed: 17482814
DOI: 10.1016/j.bmcl.2007.04.072

Experimental method

X-RAY DIFFRACTION (2 Å)