Computational insights into the binding mode of curcumin analogues against EP300 HAT domain as potent acetyltransferase inhibitors
Copyright © 2020 Elsevier Inc. All rights reserved..
Acetylation plays a key role in maintaining and balancing cellular regulation and homeostasis. Acetyltransferases are an important class of enzymes which mediate this acetylation process. EP300 is a type 3 major lysine (K) acetyl transferase, and its aberrant activity is implicated in many human diseases. Hence, targeting EP300 mediated acetylation is a necessary step to control the associated diseases. Currently, a few EP300 inhibitors are known, among which curcumin is the most widely investigated molecule. However, due to its instability, chemical aggregation and reactivity, its inhibitory activity against the EP300 acetyltransferase domain is disputable. To address this curcumin problem, different curcumin analogues have been synthesized. These molecules were selected for screening against the EP300 acetyltransferase domain using in silico docking and MD analysis. We have successfully elucidated that the curcumin analogue CNB001 is a potential EP300 inhibitor with good drug-like characteristics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:101 |
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| Enthalten in: |
Journal of molecular graphics & modelling - 101(2020) vom: 10. Dez., Seite 107756 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kandagalla, Shivananda [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.06.2021 Date Revised 21.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jmgm.2020.107756 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Computational insights into the binding mode of curcumin analogues against EP300 HAT domain as potent acetyltransferase inhibitors |
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| 500 | |a Date Revised 21.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a Acetylation plays a key role in maintaining and balancing cellular regulation and homeostasis. Acetyltransferases are an important class of enzymes which mediate this acetylation process. EP300 is a type 3 major lysine (K) acetyl transferase, and its aberrant activity is implicated in many human diseases. Hence, targeting EP300 mediated acetylation is a necessary step to control the associated diseases. Currently, a few EP300 inhibitors are known, among which curcumin is the most widely investigated molecule. However, due to its instability, chemical aggregation and reactivity, its inhibitory activity against the EP300 acetyltransferase domain is disputable. To address this curcumin problem, different curcumin analogues have been synthesized. These molecules were selected for screening against the EP300 acetyltransferase domain using in silico docking and MD analysis. We have successfully elucidated that the curcumin analogue CNB001 is a potential EP300 inhibitor with good drug-like characteristics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CNB001 | |
| 650 | 4 | |a Curcumin analogues | |
| 650 | 4 | |a Docking | |
| 650 | 4 | |a EP300 | |
| 650 | 4 | |a HAT domain | |
| 650 | 4 | |a Molecular dynamics | |
| 650 | 7 | |a Acetyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.3.1.- |2 NLM | |
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| 650 | 7 | |a EP300 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.3.1.48 |2 NLM | |
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| 700 | 1 | |a Shekarappa, Sharath Belenahalli |e verfasserin |4 aut | |
| 700 | 1 | |a Rimac, Hrvoje |e verfasserin |4 aut | |
| 700 | 1 | |a Grishina, Maria A |e verfasserin |4 aut | |
| 700 | 1 | |a Potemkin, Vladimir A |e verfasserin |4 aut | |
| 700 | 1 | |a Hanumanthappa, Manjunatha |e verfasserin |4 aut | |
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