1FKN

Structure of Beta-Secretase Complexed with Inhibitor

Summary for 1FKN

• Entry DOI: 10.2210/pdb1fkn/pdb
• Related PRD ID: PRD_000290
• Descriptor: MEMAPSIN 2, inhibitor (3 entities in total)
• Functional Keywords: alzheimer's disease, beta-secretase, memapsin 2, base, aspartic protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 4
• Total formula weight: 89040.37

Authors

Hong, L.,Koelsch, G.,Lin, X.,Wu, S.,Terzyan, S.,Ghosh, A.,Zhang, X.C.,Tang, J. (deposition date: 2000-08-09, release date: 2000-10-09, Last modification date: 2024-10-16)

Primary citation

Hong, L.,Koelsch, G.,Lin, X.,Wu, S.,Terzyan, S.,Ghosh, A.K.,Zhang, X.C.,Tang, J.
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.
Science, 290:150-153, 2000

PubMed Abstract: Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.

PubMed: 11021803
DOI: 10.1126/science.290.5489.150

Experimental method

X-RAY DIFFRACTION (1.9 Å)