Back to Search
Start Over
Mechanistics of pH-Dependent Sulfmyoglobin Formation: Spin Control and His64 Proton Relay.
- Source :
- Journal of Chemistry; 2/21/2024, Vol. 2024, p1-14, 14p
- Publication Year :
- 2024
-
Abstract
- The chemistry of hydrogen sulfide (H<subscript>2</subscript>S) 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 H<subscript>2</subscript>S. 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 H<subscript>2</subscript>S, where not all heme groups form sulfheme. The data also show that, for the reaction of oxy-myoglobin (oxy-Mb) and H<subscript>2</subscript>S, 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 His64<subscript>εδ</subscript>, 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 His64<subscript>εδ</subscript> (pH 5.0) reacts with H<subscript>2</subscript>S 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 His64<subscript>εδ</subscript>, heme Fe(II)O<subscript>2</subscript>, and H<subscript>2</subscript>S. The results establish an energetically favored quantitative mechanism to produce sulfMb (−69.1 kcal/mol) from the reactions of oxy-Mb and H<subscript>2</subscript>S. Curiously, the mechanism between met-aquo Mb, H<subscript>2</subscript>O<subscript>2</subscript>, and H<subscript>2</subscript>S 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<superscript>•</superscript>, is the species attacking the β-β double bond of heme pyrrole B, leading to the sulfheme structure. [ABSTRACT FROM AUTHOR]
- Subjects :
- MYOGLOBIN
HEMOPROTEINS
CHARGE transfer
DOUBLE bonds
HEME
HYDROGEN bonding
Subjects
Details
- Language :
- English
- ISSN :
- 20909063
- Volume :
- 2024
- Database :
- Complementary Index
- Journal :
- Journal of Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 175634250
- Full Text :
- https://doi.org/10.1155/2024/4244579