Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.
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Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC, Tang J
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.
Science. 2000 Oct 6;290(5489):150-3.
- PubMed ID
- 11021803 [ View in 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.