3BUG

BACE-1 complexed with compound 3

Summary for 3BUG

• Entry DOI: 10.2210/pdb3bug/pdb
• Related: 3BRA 3BUF 3BUH
• Descriptor: BETA-SECRETASE 1, 4-(2-aminoethyl)-2-ethylphenol (3 entities in total)
• Functional Keywords: alzheimer's disease, aspartic protease, beta-secretase, memapsin 2, fragment screen, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, transmembrane, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 45719.24

Authors

Kuglstatter, A.,Hennig, M. (deposition date: 2008-01-02, release date: 2008-03-11, Last modification date: 2024-10-30)

Primary citation

Kuglstatter, A.,Stahl, M.,Peters, J.U.,Huber, W.,Stihle, M.,Schlatter, D.,Benz, J.,Ruf, A.,Roth, D.,Enderle, T.,Hennig, M.
Tyramine fragment binding to BACE-1
Bioorg.Med.Chem.Lett., 18:1304-1307, 2008

PubMed Abstract: Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.

PubMed: 18226904
DOI: 10.1016/j.bmcl.2008.01.032

Experimental method

X-RAY DIFFRACTION (2.5 Å)