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Wild-Type Sperm Whale Myoglobin in Complex with Nitrosobenzene
Structural highlights
FunctionMYG_PHYMC Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Publication Abstract from PubMedPhenylhydroxylamine (PhNHOH) and nitrosobenzene (PhNO) interact with human tetrameric hemoglobin (Hb) to form the nitrosobenzene adduct Hb(PhNO). These interactions also frequently lead to methemoglobin formation in red blood cells. We utilize UV-vis spectroscopy and X-ray crystallography to identify the primary and secondary products that form when PhNHOH and related alkylhydroxylamines (RNHOH; R = Me, t-Bu) react with human ferric Hb. We show that with MeNHOH, the primary product is Hb[alpha-Fe(III)(H(2)O)][beta-Fe(II)(MeNO)], in which nitrosomethane is bound to the beta subunit but not the alpha subunit. Attempts to isolate a nitrosochloramphenicol (CAMNO) adduct resulted in our isolation of a Hb[alpha-Fe(II)][beta-Fe(II)-cySOx](CAMNO) product (cySOx = oxidized cysteine) in which CAMNO was located outside of the protein in the solvent region between the beta2 and alpha2 subunits of the same tetramer. We also observed that the betacys93 residue had been oxidized. In the case of t-BuNHOH, we demonstrate that the isolated product is the beta-hemichrome Hb[alpha-Fe(III)(H(2)O)][beta-Fe(III)(His)(2)](t-BuNHOH), in which the beta heme has slipped approximately 4.4 A towards the solvent exterior to accommodate the bis-His heme coordination. When PhNHOH is used, a similar beta-hemichrome Hb[alpha-Fe(III)(H(2)O)][beta-Fe(III)(His)(2)-cySOx](PhNHOH) was obtained. Our results reveal, for the first time, the X-ray structural determination of a beta-hemichrome in a human Hb derivative. Our UV-vis and X-ray crystal structural result reveal that although Hb(PhNO) and Hb(RNO) complexes may form as primary products, attempted isolation of these products by crystallization may result in the structural determination of their secondary products which may contain beta-hemichromes en route to further protein degradation. Crystal structural investigations of heme protein derivatives resulting from reactions of aryl- and alkylhydroxylamines with human hemoglobin.,Powell SM, Wang B, Herrera VE, Prather KY, Nguyen NT, Abucayon EG, Thomas LM, Safo MK, Richter-Addo GB J Inorg Biochem. 2023 Sep;246:112304. doi: 10.1016/j.jinorgbio.2023.112304. Epub , 2023 Jun 25. PMID:37406385[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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