In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes
Background: Neurodegenerative diseases can cause vision loss by damaging retinal ganglion cells in the optic nerve. Novel phosphine-borane compounds (PBs) can protect these cells from oxidative stress via the reduction of disulfide bonds. However, the specific targets of these compounds are unknown....
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MDPI AG
2024-10-01
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| author | Raheem Remtulla Sanjoy Kumar Das Leonard A. Levin |
| author_facet | Raheem Remtulla Sanjoy Kumar Das Leonard A. Levin |
| author_sort | Raheem Remtulla |
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| description | Background: Neurodegenerative diseases can cause vision loss by damaging retinal ganglion cells in the optic nerve. Novel phosphine-borane compounds (PBs) can protect these cells from oxidative stress via the reduction of disulfide bonds. However, the specific targets of these compounds are unknown. Proteomic evidence suggests that myelin oligodendrocyte glycoprotein (MOG) is a potential target. MOG is of significant interest due to its role in anti-MOG optic neuritis syndrome. Methods: We used in silico modeling to explore the structural consequences of cleaving the extracellular domain MOG disulfide bond, both in isolation and in complex with anti-MOG antibodies. The potential binding of PBs to this bond was examined using molecular docking. Results: Cleaving the disulfide bond of MOG altered the structure of MOG dimers and reduced their energetic favorability by 46.13 kcal/mol. The energy profiles of anti-MOG antibody complexes were less favorable when the disulfide bond of MOG was reduced in the monomeric state by 55.21 kcal/mol, but the reverse was true in the dimeric state. PBs exhibited reducing capabilities with the MOG extracellular disulfide bond, with this best-scoring compound binding with an energy of −28.54 kcal/mol to the MOG monomer and −24.97 kcal/mol to the MOG dimer. Conclusions: These findings suggest that PBs can affect the structure of MOG dimers and the formation of antibody complexes by reducing the MOG disulfide bond. Structural changes in MOG could have implications for neurodegenerative diseases and anti-MOG syndrome. |
| format | Article |
| id | doaj-art-8fa3fe4636d54c968a203051db3e5b84 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-8fa3fe4636d54c968a203051db3e5b842025-08-20T02:48:02ZengMDPI AGPharmaceuticals1424-82472024-10-011711141710.3390/ph17111417In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane ComplexesRaheem Remtulla0Sanjoy Kumar Das1Leonard A. Levin2Department of Ophthalmology and Visual Sciences, McGill University, Montreal, QC H3A 0G4, CanadaDivision of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, CanadaDepartment of Ophthalmology and Visual Sciences, McGill University, Montreal, QC H3A 0G4, CanadaBackground: Neurodegenerative diseases can cause vision loss by damaging retinal ganglion cells in the optic nerve. Novel phosphine-borane compounds (PBs) can protect these cells from oxidative stress via the reduction of disulfide bonds. However, the specific targets of these compounds are unknown. Proteomic evidence suggests that myelin oligodendrocyte glycoprotein (MOG) is a potential target. MOG is of significant interest due to its role in anti-MOG optic neuritis syndrome. Methods: We used in silico modeling to explore the structural consequences of cleaving the extracellular domain MOG disulfide bond, both in isolation and in complex with anti-MOG antibodies. The potential binding of PBs to this bond was examined using molecular docking. Results: Cleaving the disulfide bond of MOG altered the structure of MOG dimers and reduced their energetic favorability by 46.13 kcal/mol. The energy profiles of anti-MOG antibody complexes were less favorable when the disulfide bond of MOG was reduced in the monomeric state by 55.21 kcal/mol, but the reverse was true in the dimeric state. PBs exhibited reducing capabilities with the MOG extracellular disulfide bond, with this best-scoring compound binding with an energy of −28.54 kcal/mol to the MOG monomer and −24.97 kcal/mol to the MOG dimer. Conclusions: These findings suggest that PBs can affect the structure of MOG dimers and the formation of antibody complexes by reducing the MOG disulfide bond. Structural changes in MOG could have implications for neurodegenerative diseases and anti-MOG syndrome.https://www.mdpi.com/1424-8247/17/11/1417phosphine-borane complexesmyelin oligodendrocyte glycoproteindisulfide bondsbond cleavingoptic neuritisneurodegeneration |
| spellingShingle | Raheem Remtulla Sanjoy Kumar Das Leonard A. Levin In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes Pharmaceuticals phosphine-borane complexes myelin oligodendrocyte glycoprotein disulfide bonds bond cleaving optic neuritis neurodegeneration |
| title | In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes |
| title_full | In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes |
| title_fullStr | In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes |
| title_full_unstemmed | In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes |
| title_short | In Silico Modeling of Myelin Oligodendrocyte Glycoprotein Disulfide Bond Reduction by Phosphine-Borane Complexes |
| title_sort | in silico modeling of myelin oligodendrocyte glycoprotein disulfide bond reduction by phosphine borane complexes |
| topic | phosphine-borane complexes myelin oligodendrocyte glycoprotein disulfide bonds bond cleaving optic neuritis neurodegeneration |
| url | https://www.mdpi.com/1424-8247/17/11/1417 |
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