Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L.
REPI is a pivotal point enzyme in plant benzylisoquinoline alkaloid metabolism as it promotes the evolution of the biosynthetic branch of morphinan alkaloids. Experimental studies of its activity led to the identification of two modules (DRS and DRR) that catalyze two sequential steps of the epimeri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/1/2 |
| _version_ | 1797344548609851392 |
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| author | Alba Diaz-Bárcena Luis Fernandez-Pacios Patricia Giraldo |
| author_facet | Alba Diaz-Bárcena Luis Fernandez-Pacios Patricia Giraldo |
| author_sort | Alba Diaz-Bárcena |
| collection | DOAJ |
| description | REPI is a pivotal point enzyme in plant benzylisoquinoline alkaloid metabolism as it promotes the evolution of the biosynthetic branch of morphinan alkaloids. Experimental studies of its activity led to the identification of two modules (DRS and DRR) that catalyze two sequential steps of the epimerization of (S)- to (R)-reticuline. Recently, special attention has been paid to its genetic characterization and evolutionary history, but no structural analyses of the REPI protein have been conducted to date. We present here a computational structural characterization of REPI with heme and NADP cofactors in the apo state and in three complexes with substrate (S)-reticuline in DRS and intermediate 1,2-dehydroreticuline in DRS and in DRR. Since no experimental structure exists for REPI, we used its AlphaFold model as a scaffold to build up these four systems, which were submitted to all-atom molecular dynamics (MD) simulations. A comparison of MD results for the four systems revealed key dynamic changes associated with cofactor and ligand binding and provided a dynamic picture of the evolution of their structures and interactions. We also explored the possible dynamic occurrence of tunnels and electrostatic highways potentially involved in alternative mechanisms for channeling the intermediate from DRS to DRR. |
| first_indexed | 2024-03-08T11:04:20Z |
| format | Article |
| id | doaj.art-634bff69299249f6a42b7ef13f47884f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-08T11:04:20Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-634bff69299249f6a42b7ef13f47884f2024-01-26T15:17:18ZengMDPI AGBiomolecules2218-273X2023-12-01141210.3390/biom14010002Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L.Alba Diaz-Bárcena0Luis Fernandez-Pacios1Patricia Giraldo2Department of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid, 28040 Madrid, SpainDepartment of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid, 28040 Madrid, SpainDepartment of Biotechnology-Plant Biology, School of Agricultural, Food and Biosystems Engineering, Universidad Politécnica de Madrid, 28040 Madrid, SpainREPI is a pivotal point enzyme in plant benzylisoquinoline alkaloid metabolism as it promotes the evolution of the biosynthetic branch of morphinan alkaloids. Experimental studies of its activity led to the identification of two modules (DRS and DRR) that catalyze two sequential steps of the epimerization of (S)- to (R)-reticuline. Recently, special attention has been paid to its genetic characterization and evolutionary history, but no structural analyses of the REPI protein have been conducted to date. We present here a computational structural characterization of REPI with heme and NADP cofactors in the apo state and in three complexes with substrate (S)-reticuline in DRS and intermediate 1,2-dehydroreticuline in DRS and in DRR. Since no experimental structure exists for REPI, we used its AlphaFold model as a scaffold to build up these four systems, which were submitted to all-atom molecular dynamics (MD) simulations. A comparison of MD results for the four systems revealed key dynamic changes associated with cofactor and ligand binding and provided a dynamic picture of the evolution of their structures and interactions. We also explored the possible dynamic occurrence of tunnels and electrostatic highways potentially involved in alternative mechanisms for channeling the intermediate from DRS to DRR.https://www.mdpi.com/2218-273X/14/1/2<i>Papaver somniferum</i>REPISTORRprotein structural modelingmolecular dynamicselectrostatic potential |
| spellingShingle | Alba Diaz-Bárcena Luis Fernandez-Pacios Patricia Giraldo Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. Biomolecules <i>Papaver somniferum</i> REPI STORR protein structural modeling molecular dynamics electrostatic potential |
| title | Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. |
| title_full | Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. |
| title_fullStr | Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. |
| title_full_unstemmed | Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. |
| title_short | Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from <i>Papaver somniferum</i> L. |
| title_sort | structural characterization and molecular dynamics study of the repi fusion protein from i papaver somniferum i l |
| topic | <i>Papaver somniferum</i> REPI STORR protein structural modeling molecular dynamics electrostatic potential |
| url | https://www.mdpi.com/2218-273X/14/1/2 |
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