Structure of puromycin-sensitive aminopeptidase and polyglutamine binding.
Puromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 Ǻ. Overall, the en...
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287086&type=printable |
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| author | Sowmya Madabushi K Martin Chow Eun Suk Song Anwesha Goswami Louis B Hersh David W Rodgers |
| author_facet | Sowmya Madabushi K Martin Chow Eun Suk Song Anwesha Goswami Louis B Hersh David W Rodgers |
| author_sort | Sowmya Madabushi |
| collection | DOAJ |
| description | Puromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 Ǻ. Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation. |
| format | Article |
| id | doaj-art-3b2f3daab1ff45f786b376cc55adf2b0 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3b2f3daab1ff45f786b376cc55adf2b02025-08-20T02:12:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01187e028708610.1371/journal.pone.0287086Structure of puromycin-sensitive aminopeptidase and polyglutamine binding.Sowmya MadabushiK Martin ChowEun Suk SongAnwesha GoswamiLouis B HershDavid W RodgersPuromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 Ǻ. Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287086&type=printable |
| spellingShingle | Sowmya Madabushi K Martin Chow Eun Suk Song Anwesha Goswami Louis B Hersh David W Rodgers Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. PLoS ONE |
| title | Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. |
| title_full | Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. |
| title_fullStr | Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. |
| title_full_unstemmed | Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. |
| title_short | Structure of puromycin-sensitive aminopeptidase and polyglutamine binding. |
| title_sort | structure of puromycin sensitive aminopeptidase and polyglutamine binding |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287086&type=printable |
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