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Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase.
Bhagi-Damodaran, Ambika; Reed, Julian H; Zhu, Qianhong; Shi, Yelu; Hosseinzadeh, Parisa; Sandoval, Braddock A; Harnden, Kevin A; Wang, Shuyan; Sponholtz, Madeline R; Mirts, Evan N; Dwaraknath, Sudharsan; Zhang, Yong; Moënne-Loccoz, Pierre; Lu, Yi.
Afiliación
  • Bhagi-Damodaran A; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Reed JH; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Zhu Q; Division of Environmental & Biomolecular Systems, Oregon Health & Science University, Portland, OR 97239.
  • Shi Y; Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030.
  • Hosseinzadeh P; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Sandoval BA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Harnden KA; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Wang S; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Sponholtz MR; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Mirts EN; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Dwaraknath S; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Zhang Y; Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030; yi-lu@illinois.edu yong.zhang@stevens.edu moennelo@ohsu.edu.
  • Moënne-Loccoz P; Division of Environmental & Biomolecular Systems, Oregon Health & Science University, Portland, OR 97239; yi-lu@illinois.edu yong.zhang@stevens.edu moennelo@ohsu.edu.
  • Lu Y; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801; yi-lu@illinois.edu yong.zhang@stevens.edu moennelo@ohsu.edu.
Proc Natl Acad Sci U S A ; 115(24): 6195-6200, 2018 06 12.
Article en En | MEDLINE | ID: mdl-29802230
Despite 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°') 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°' 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°' on NO reduction. Decreasing E°' 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°' 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°' and fast electron transfer facilitated by high E°'. Only when E°' 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°' in a similar range as NORs (between -59 and 200 mV) exhibit NOR reactivity. Thus, our work demonstrates efficient tuning of E°' in various metalloproteins for their optimal functionality.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidorreductasas / Hemo Tipo de estudio: Prognostic_studies Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidorreductasas / Hemo Tipo de estudio: Prognostic_studies Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos