1XS7

Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).

Summary for 1XS7

• Entry DOI: 10.2210/pdb1xs7/pdb
• Descriptor: Beta-secretase 1, N-[(4S,5S,7R)-8-({(S)-1-[(BENZYLAMINO)OXOMETHYL]-2-METHYLPROPYL}AMINO)-5-HYDROXY-2,7-DIMETHYL-8-OXO-OCT-4-YL]-(4S,7S)-4 -ISOPROPYL-2,5,9-TRIOXO-1-OXA-3,6,10-TRIAZACYCLOHEXADECANE-7-CARBOXAMIDE (2 entities in total)
• Functional Keywords: beta secretase, memapsin2, bace, asp2, aspartic protease, acid protease, alzheimer's disease, drug design, 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: 44043.74

Authors

Ghosh, A.,Devasamudram, T.,Hong, L.,DeZutter, C.,Xu, X.,Weerasena, V.,Koelsch, G.,Bilcer, G.,Tang, J. (deposition date: 2004-10-18, release date: 2004-12-21, Last modification date: 2024-11-13)

Primary citation

Ghosh, A.K.,Devasamudram, T.,Hong, L.,Dezutter, C.,Xu, X.,Weerasena, V.,Koelsch, G.,Bilcer, G.,Tang, J.
Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).
Bioorg.Med.Chem.Lett., 15:15-20, 2005

PubMed Abstract: A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).

PubMed: 15582402
DOI: 10.1016/j.bmcl.2004.10.084

Experimental method

X-RAY DIFFRACTION (2.8 Å)