Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay
The chemistry of hydrogen sulfide (H2S) has been directed towards physiologically relevant hemeproteins, including myoglobin, hemoglobin, and other similar proteins. Despite substantial efforts, there remains a need to elucidate the mechanism and identify the species involved in the reaction between...
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| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2024/4244579 |
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| author | Angel D. Rodriguez-Mackenzie Lysmarie Santos-Velazquez Héctor D. Arbelo-Lopez Troy Wymore Juan Lopez-Garriga |
| author_facet | Angel D. Rodriguez-Mackenzie Lysmarie Santos-Velazquez Héctor D. Arbelo-Lopez Troy Wymore Juan Lopez-Garriga |
| author_sort | Angel D. Rodriguez-Mackenzie |
| collection | DOAJ |
| description | The chemistry of hydrogen sulfide (H2S) has been directed towards physiologically relevant hemeproteins, including myoglobin, hemoglobin, and other similar proteins. Despite substantial efforts, there remains a need to elucidate the mechanism and identify the species involved in the reaction between oxy-hemeproteins and H2S. Here, we summarize both our experimental data and computational modeling results revealing the mechanisms by which sulfmyoglobin (sulfMb) and sulfhemoglobin (sulfHb) are formed. Our experimental data at pH 7.4 reveal differences in intensity between sulfMb and sulfHb chromophores in the 620 nm charge transfer region. This behavior could be attributed to the incomplete reaction of tetrameric oxy-Hb with H2S, where not all heme groups form sulfheme. The data also show that, for the reaction of oxy-myoglobin (oxy-Mb) and H2S, the 622 nm charge transfer band increases in intensity from a pH of 6.6 to 5.0. This increase is attributed to the presence of the heme pocket distal His64εδ, which is positively charged, resulting in an elevated yield of sulfMb formation compared to the mono-protonated tautomer, His64ε. Computational hybrid QM/MM methods support the conclusion, indicating that oxy-Mb His64εδ (pH 5.0) reacts with H2S in the triplet state, favored by −31.0 kcal/mol over the singlet His64ε (pH 6.6) species. The phenomenon is facilitated by a hydrogen bonding network within the heme pocket, between His64εδ, heme Fe(II)O2, and H2S. The results establish an energetically favored quantitative mechanism to produce sulfMb (−69.1 kcal/mol) from the reactions of oxy-Mb and H2S. Curiously, the mechanism between met-aquo Mb, H2O2, and H2S shows similar reaction pathways and leads to sulfheme formation (−135.3 kcal/mol). The energetic barrier towards intermediate Cpd-0 is the limiting step in sulfheme formation for both systems. Both mechanisms show that the thiyl radical, HS•, is the species attacking the β-β double bond of heme pyrrole B, leading to the sulfheme structure. |
| format | Article |
| id | doaj-art-577ffc3ecb4e4930b20b40fb4e6fc6bd |
| institution | Kabale University |
| issn | 2090-9071 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
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| series | Journal of Chemistry |
| spelling | doaj-art-577ffc3ecb4e4930b20b40fb4e6fc6bd2025-08-20T03:33:36ZengWileyJournal of Chemistry2090-90712024-01-01202410.1155/2024/4244579Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton RelayAngel D. Rodriguez-Mackenzie0Lysmarie Santos-Velazquez1Héctor D. Arbelo-Lopez2Troy Wymore3Juan Lopez-Garriga4Department of ChemistryDepartment of ChemistryDepartment of ChemistryLaufer Center Stony Brook UniversityDepartment of ChemistryThe chemistry of hydrogen sulfide (H2S) has been directed towards physiologically relevant hemeproteins, including myoglobin, hemoglobin, and other similar proteins. Despite substantial efforts, there remains a need to elucidate the mechanism and identify the species involved in the reaction between oxy-hemeproteins and H2S. Here, we summarize both our experimental data and computational modeling results revealing the mechanisms by which sulfmyoglobin (sulfMb) and sulfhemoglobin (sulfHb) are formed. Our experimental data at pH 7.4 reveal differences in intensity between sulfMb and sulfHb chromophores in the 620 nm charge transfer region. This behavior could be attributed to the incomplete reaction of tetrameric oxy-Hb with H2S, where not all heme groups form sulfheme. The data also show that, for the reaction of oxy-myoglobin (oxy-Mb) and H2S, the 622 nm charge transfer band increases in intensity from a pH of 6.6 to 5.0. This increase is attributed to the presence of the heme pocket distal His64εδ, which is positively charged, resulting in an elevated yield of sulfMb formation compared to the mono-protonated tautomer, His64ε. Computational hybrid QM/MM methods support the conclusion, indicating that oxy-Mb His64εδ (pH 5.0) reacts with H2S in the triplet state, favored by −31.0 kcal/mol over the singlet His64ε (pH 6.6) species. The phenomenon is facilitated by a hydrogen bonding network within the heme pocket, between His64εδ, heme Fe(II)O2, and H2S. The results establish an energetically favored quantitative mechanism to produce sulfMb (−69.1 kcal/mol) from the reactions of oxy-Mb and H2S. Curiously, the mechanism between met-aquo Mb, H2O2, and H2S shows similar reaction pathways and leads to sulfheme formation (−135.3 kcal/mol). The energetic barrier towards intermediate Cpd-0 is the limiting step in sulfheme formation for both systems. Both mechanisms show that the thiyl radical, HS•, is the species attacking the β-β double bond of heme pyrrole B, leading to the sulfheme structure.http://dx.doi.org/10.1155/2024/4244579 |
| spellingShingle | Angel D. Rodriguez-Mackenzie Lysmarie Santos-Velazquez Héctor D. Arbelo-Lopez Troy Wymore Juan Lopez-Garriga Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay Journal of Chemistry |
| title | Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay |
| title_full | Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay |
| title_fullStr | Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay |
| title_full_unstemmed | Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay |
| title_short | Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay |
| title_sort | mechanistics of ph dependent sulfmyoglobin formation spin control and his64 proton relay |
| url | http://dx.doi.org/10.1155/2024/4244579 |
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