Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration
The protease HTRA1 is a genetic risk factor for geographic atrophy. Here, Gerhardy et al. describe its inhibition by a clinical Fab, whose binding locks it in an inactive state. The mechanism identifies an essential function of LoopA with this protease family.
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-32760-9 |
| _version_ | 1818064631249240064 |
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| author | Stefan Gerhardy Mark Ultsch Wanjian Tang Evan Green Jeffrey K. Holden Wei Li Alberto Estevez Chris Arthur Irene Tom Alexis Rohou Daniel Kirchhofer |
| author_facet | Stefan Gerhardy Mark Ultsch Wanjian Tang Evan Green Jeffrey K. Holden Wei Li Alberto Estevez Chris Arthur Irene Tom Alexis Rohou Daniel Kirchhofer |
| author_sort | Stefan Gerhardy |
| collection | DOAJ |
| description | The protease HTRA1 is a genetic risk factor for geographic atrophy. Here, Gerhardy et al. describe its inhibition by a clinical Fab, whose binding locks it in an inactive state. The mechanism identifies an essential function of LoopA with this protease family. |
| first_indexed | 2024-12-10T14:39:04Z |
| format | Article |
| id | doaj.art-55461e6817b145b7b4f3d1b202ec723c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-10T14:39:04Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-55461e6817b145b7b4f3d1b202ec723c2022-12-22T01:44:45ZengNature PortfolioNature Communications2041-17232022-09-0113111610.1038/s41467-022-32760-9Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degenerationStefan Gerhardy0Mark Ultsch1Wanjian Tang2Evan Green3Jeffrey K. Holden4Wei Li5Alberto Estevez6Chris Arthur7Irene Tom8Alexis Rohou9Daniel Kirchhofer10Department of Early Discovery Biochemistry, Genentech Inc.Department of Structural Biology, Genentech Inc.Department of Early Discovery Biochemistry, Genentech Inc.Department of Structural Biology, Genentech Inc.Department of Early Discovery Biochemistry, Genentech Inc.Department of Early Discovery Biochemistry, Genentech Inc.Department of Structural Biology, Genentech Inc.Department of Structural Biology, Genentech Inc.Department of OMNI Biomarker Development, Genentech Inc.Department of Structural Biology, Genentech Inc.Department of Early Discovery Biochemistry, Genentech Inc.The protease HTRA1 is a genetic risk factor for geographic atrophy. Here, Gerhardy et al. describe its inhibition by a clinical Fab, whose binding locks it in an inactive state. The mechanism identifies an essential function of LoopA with this protease family.https://doi.org/10.1038/s41467-022-32760-9 |
| spellingShingle | Stefan Gerhardy Mark Ultsch Wanjian Tang Evan Green Jeffrey K. Holden Wei Li Alberto Estevez Chris Arthur Irene Tom Alexis Rohou Daniel Kirchhofer Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration Nature Communications |
| title | Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration |
| title_full | Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration |
| title_fullStr | Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration |
| title_full_unstemmed | Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration |
| title_short | Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration |
| title_sort | allosteric inhibition of htra1 activity by a conformational lock mechanism to treat age related macular degeneration |
| url | https://doi.org/10.1038/s41467-022-32760-9 |
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