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| Formato: | Artículo Open Access |
| Publicado: |
Wiley
2024
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| Acceso en línea: | https://onlinelibrary.wiley.com/doi/10.1002/pro.4921 |
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| author | Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák |
| author_facet | Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák |
| collection | Wiley Open Access |
| contents | Design of AsLOV2 domain as a carrier of light‐induced dissociable FMN photosensitizer Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák Protein Science AbstractFlavin mononucleotide (FMN) is a highly efficient photosensitizer (PS) yielding singlet oxygen (1O2). However, its 1O2 production efficiency significantly decreases upon isoalloxazine ring encapsulation into the protein matrix in genetically encoded photosensitizers (GEPS). Reducing isoalloxazine ring interactions with surrounding amino acids by protein engineering may increase 1O2 production efficiency GEPS, but at the same time weakened native FMN–protein interactions may cause undesirable FMN dissociation. Here, in contrast, we intentionally induce the FMN release by light‐triggered sulfur oxidation of strategically placed cysteines (oxidation‐prone amino acids) in the isoalloxazine‐binding site due to significantly increased volume of the cysteinyl side residue(s). As a proof of concept, in three variants of the LOV2 domain of Avena sativa (AsLOV2), namely V416C, T418C, and V416C/T418C, the effective 1O2 production strongly correlated with the efficiency of irradiation‐induced FMN dissociation (wild type (WT) < V416C < T418C < V416C/T418C). This alternative approach enables us: (i) to overcome the low 1O2 production efficiency of flavin‐based GEPSs without affecting native isoalloxazine ring‐protein interactions and (ii) to utilize AsLOV2, due to its inherent binding propensity to FMN, as a PS vehicle, which is released at a target by light irradiation. 10.1002/pro.4921 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/pro.4921 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_pro_4921 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Design of AsLOV2 domain as a carrier of light‐induced dissociable FMN photosensitizer Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák Protein Science Design of AsLOV2 domain as a carrier of light‐induced dissociable FMN photosensitizer Kristína Felčíková Andrej Hovan Marek Polák Dmitry S. Loginov Veronika Holotová Carlos Díaz Tibor Kožár One‐Sun Lee Rastislav Varhač Petr Novák Gregor Bánó Erik Sedlák Protein Science AbstractFlavin mononucleotide (FMN) is a highly efficient photosensitizer (PS) yielding singlet oxygen (1O2). However, its 1O2 production efficiency significantly decreases upon isoalloxazine ring encapsulation into the protein matrix in genetically encoded photosensitizers (GEPS). Reducing isoalloxazine ring interactions with surrounding amino acids by protein engineering may increase 1O2 production efficiency GEPS, but at the same time weakened native FMN–protein interactions may cause undesirable FMN dissociation. Here, in contrast, we intentionally induce the FMN release by light‐triggered sulfur oxidation of strategically placed cysteines (oxidation‐prone amino acids) in the isoalloxazine‐binding site due to significantly increased volume of the cysteinyl side residue(s). As a proof of concept, in three variants of the LOV2 domain of Avena sativa (AsLOV2), namely V416C, T418C, and V416C/T418C, the effective 1O2 production strongly correlated with the efficiency of irradiation‐induced FMN dissociation (wild type (WT) < V416C < T418C < V416C/T418C). This alternative approach enables us: (i) to overcome the low 1O2 production efficiency of flavin‐based GEPSs without affecting native isoalloxazine ring‐protein interactions and (ii) to utilize AsLOV2, due to its inherent binding propensity to FMN, as a PS vehicle, which is released at a target by light irradiation. 10.1002/pro.4921 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Design of AsLOV2 domain as a carrier of light‐induced dissociable FMN photosensitizer |
| topic | Protein Science |
| url | https://onlinelibrary.wiley.com/doi/10.1002/pro.4921 |