6d45 | pdb_00006d45
L89S Mutant of FeBMb Sperm Whale Myoglobin
Structural highlights
Function[MYG_PHYCD] Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Publication Abstract from PubMedDespite high structural homology between NO reductases (NORs) and heme-copper oxidases (HCOs), factors governing their reaction specificity remain to be understood. Using a myoglobin-based model of NOR (FeBMb) and tuning its heme redox potentials (E degrees ') to cover the native NOR range, through manipulating hydrogen bonding to the proximal histidine ligand and replacing heme b with monoformyl (MF-) or diformyl (DF-) hemes, we herein demonstrate that the E degrees ' holds the key to reactivity differences between NOR and HCO. Detailed electrochemical, kinetic, and vibrational spectroscopic studies, in tandem with density functional theory calculations, demonstrate a strong influence of heme E degrees ' on NO reduction. Decreasing E degrees ' from +148 to -130 mV significantly impacts electronic properties of the NOR mimics, resulting in 180- and 633-fold enhancements in NO association and heme-nitrosyl decay rates, respectively. Our results indicate that NORs exhibit finely tuned E degrees ' that maximizes their enzymatic efficiency and helps achieve a balance between opposite factors: fast NO binding and decay of dinitrosyl species facilitated by low E degrees ' and fast electron transfer facilitated by high E degrees '. Only when E degrees ' is optimally tuned in FeBMb(MF-heme) for NO binding, heme-nitrosyl decay, and electron transfer does the protein achieve multiple (>35) turnovers, previously not achieved by synthetic or enzyme-based NOR models. This also explains a long-standing question in bioenergetics of selective cross-reactivity in HCOs. Only HCOs with heme E degrees ' in a similar range as NORs (between -59 and 200 mV) exhibit NOR reactivity. Thus, our work demonstrates efficient tuning of E degrees ' in various metalloproteins for their optimal functionality. Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase.,Bhagi-Damodaran A, Reed JH, Zhu Q, Shi Y, Hosseinzadeh P, Sandoval BA, Harnden KA, Wang S, Sponholtz MR, Mirts EN, Dwaraknath S, Zhang Y, Moenne-Loccoz P, Lu Y Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6195-6200. doi:, 10.1073/pnas.1720298115. Epub 2018 May 25. PMID:29802230[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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