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Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor
Abstract
Memapsin 2 (β-secretase) is a membrane-associated aspartic protease involved in the production of β-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 S 4 to S 2 ′ are well defined. A kink of the inhibitor chain at P 2 ′ and the change of chain direction of P 3 ′ and P 4 ′ may be mimicked to provide inhibitor selectivity.
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Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
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Metadata
- Authors
- Hong, L., Koelsch, G., Lin, X., Wu, S., Terzyan, S., Ghosh, A. K., Zhang, X. C., & Tang, J.
- Venue
- Science
- Published
- 2000-10-06
- Volume
- 290
- Issue
- 5489
- Pages
- 150-153
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1854324009
- Cited by
- 711
- References
- 1
- FWCI
- 18.14
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hong, L., Koelsch, G., Lin, X., Wu, S., Terzyan, S., Ghosh, A. K., Zhang, X. C., & Tang, J. (2000). Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor. Science. https://doi.org/10.1126/science.290.5489.150
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
