Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors.
Angiotensin-I converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase involved in regulating blood pressure via the kallikrein-kininand renin-angiotensin-aldosterone complex. Therefore, ACE is a key drug target for the treatment of cardiovascular system diseases. At present many works are...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0215609 |
| _version_ | 1818590364741664768 |
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| author | Li Fang Mingxian Geng Chunlei Liu Ji Wang Weihong Min Jingsheng Liu |
| author_facet | Li Fang Mingxian Geng Chunlei Liu Ji Wang Weihong Min Jingsheng Liu |
| author_sort | Li Fang |
| collection | DOAJ |
| description | Angiotensin-I converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase involved in regulating blood pressure via the kallikrein-kininand renin-angiotensin-aldosterone complex. Therefore, ACE is a key drug target for the treatment of cardiovascular system diseases. At present many works are focus on searching for new inhibitory peptides of ACE to control the blood pressure. In order to exploit the interactions between ACE and its inhibitors, molecular dynamics simulations were used. The results showed that (a) the secondary structures of the three inhibitor-protein complexes did not change significantly; (b) root-mean-square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA) values of Leu-Ile-Val-Thr (LIVT)-ACE complexes were significantly higher than that of other systems; (c) the backbone movement of LIVT was vigorous in Asp300-Val350, compared with that in Tyr-Leu-Val-Pro-His (YLVPH) and Tyr-Leu-Val-Arg(YLVR), as shown by the center-of-mass distance; and (d) the backbone movement of Asp300-Val350 may contribute to the interaction between ACE and its inhibitors. Our theoretical results will be helpful to further the design of specific inhibitors of ACE. |
| first_indexed | 2024-12-16T09:55:22Z |
| format | Article |
| id | doaj.art-a4b77216bd3441c0b6f2c242545def87 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:55:22Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a4b77216bd3441c0b6f2c242545def872022-12-21T22:35:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021560910.1371/journal.pone.0215609Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors.Li FangMingxian GengChunlei LiuJi WangWeihong MinJingsheng LiuAngiotensin-I converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase involved in regulating blood pressure via the kallikrein-kininand renin-angiotensin-aldosterone complex. Therefore, ACE is a key drug target for the treatment of cardiovascular system diseases. At present many works are focus on searching for new inhibitory peptides of ACE to control the blood pressure. In order to exploit the interactions between ACE and its inhibitors, molecular dynamics simulations were used. The results showed that (a) the secondary structures of the three inhibitor-protein complexes did not change significantly; (b) root-mean-square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA) values of Leu-Ile-Val-Thr (LIVT)-ACE complexes were significantly higher than that of other systems; (c) the backbone movement of LIVT was vigorous in Asp300-Val350, compared with that in Tyr-Leu-Val-Pro-His (YLVPH) and Tyr-Leu-Val-Arg(YLVR), as shown by the center-of-mass distance; and (d) the backbone movement of Asp300-Val350 may contribute to the interaction between ACE and its inhibitors. Our theoretical results will be helpful to further the design of specific inhibitors of ACE.https://doi.org/10.1371/journal.pone.0215609 |
| spellingShingle | Li Fang Mingxian Geng Chunlei Liu Ji Wang Weihong Min Jingsheng Liu Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. PLoS ONE |
| title | Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. |
| title_full | Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. |
| title_fullStr | Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. |
| title_full_unstemmed | Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. |
| title_short | Structural and molecular basis of angiotensin-converting enzyme by computational modeling: Insights into the mechanisms of different inhibitors. |
| title_sort | structural and molecular basis of angiotensin converting enzyme by computational modeling insights into the mechanisms of different inhibitors |
| url | https://doi.org/10.1371/journal.pone.0215609 |
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