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.
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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.
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| uniprot:name |
Science
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| uniprot:author |
Ghosh A.K.,
Hong L.,
Koelsch G.,
Lin X.,
Tang J.,
Terzyan S.,
Wu S.,
Zhang X.C.
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| uniprot:date |
2000
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| uniprot:pages |
150-153
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| uniprot:title |
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.
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| uniprot:volume |
290
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| dc-term:identifier |
doi:10.1126/science.290.5489.150
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