Atomistic Insights into Photoprotein Formation : Computational Prediction of the Properties of Coelenterazine and Oxygen Binding in Obelin
© 2019 Wiley Periodicals, Inc.
| Publié dans: | Journal of computational chemistry. - 1984. - 41(2020), 6 vom: 05. März, Seite 587-603 |
|---|---|
| Auteur principal: | |
| Autres auteurs: | , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2020
|
| Accès à la collection: | Journal of computational chemistry |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't bioluminescence implicit ligand sampling molecular dynamics simulations oxygen binding photoprotein formation Imidazoles Luminescent Proteins Pyrazines plus... |
| Résumé: | © 2019 Wiley Periodicals, Inc. Bioluminescence in marine systems is dominated by the use of coelenterazine for light production. The bioluminescent reaction of coelenterazine is an enzyme catalyzed oxidative decarboxylation: coelenterazine reacts with molecular oxygen to form carbon dioxide, coelenteramide, and light. One such class is the Ca2+ -regulated photoproteins. These proteins bind coelenterazine and oxygen, and trap 2-hydroperoxycoelenterazine, an intermediate along the reaction pathway. The reaction is halted until Ca2+ binding triggers the completion of the reaction. There are currently no reported experimental, atomistic descriptions of this ternary Michaelis complex. This study utilized computational techniques to develop an atomistic model of the Michaelis complex. Extensive molecular dynamics simulations were carried out to study the interactions between four tautomeric/protonation states of coelenterazine and wide-type and mutant obelin. Only minor differences in binding modes were observed across all systems. Interestingly, no basic residues were identified in the vicinity of the N7-nitrogen of coelenterazine. This observation was surprising considering that deprotonation at this position is a key mechanistic step in the proposed bioluminescent reaction. This work suggests that coelenterazine binds either as the O10H tautomer, or in the deprotonated form. Implicit ligand sampling simulations were used to identify potential O2 binding and migration pathways within obelin. A key oxygen binding site was identified close to the coelenterazine imidazopyrazinone core. The O2 binding free energy was observed to be dependent on the protonation state of coelenterazine. Taken together, the description of the obelin-coelenterazine-O2 complexes established in this study provides the basis for future computational studies of the bioluminescent mechanism. © 2019 Wiley Periodicals, Inc |
|---|---|
| Description: | Date Completed 30.04.2021 Date Revised 30.04.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.26125 |