Manganese and Cobalt in the Nonheme-Metal-Binding Site of a Biosynthetic Model of Heme-Copper Oxidase Superfamily Confer Oxidase Activity through Redox-Inactive Mechanism

Julian H. Reed, Yelu Shi, Qianhong Zhu, Saumen Chakraborty, Evan N. Mirts, Igor D. Petrik, Ambika Bhagi-Damodaran, Matthew Ross, Pierre Moenne-Loccoz, Yong Zhang, Yi Lu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The presence of a nonheme metal, such as copper and iron, in the heme-copper oxidase (HCO) superfamily is critical to the enzymatic activity of reducing O2 to H2O, but the exact mechanism the nonheme metal ion uses to confer and fine-tune the activity remains to be understood. We herein report that manganese and cobalt can bind to the same nonheme site and confer HCO activity in a heme-nonheme biosynthetic model in myoglobin. While the initial rates of O2 reduction by the Mn, Fe, and Co derivatives are similar, the percentages of reactive oxygen species (ROS) formation are 7%, 4%, and 1% and the total turnovers are 5.1 ± 1.1, 13.4 ± 0.7, and 82.5 ± 2.5, respectively. These results correlate with the trends of nonheme-metal-binding dissociation constants (35, 22, and 9 μM) closely, suggesting that tighter metal binding can prevent ROS release from the active site, lessen damage to the protein, and produce higher total turnover numbers. Detailed spectroscopic, electrochemical, and computational studies found no evidence of redox cycling of manganese or cobalt in the enzymatic reactions and suggest that structural and electronic effects related to the presence of different nonheme metals lead to the observed differences in reactivity. This study of the roles of nonheme metal ions beyond the Cu and Fe found in native enzymes has provided deeper insights into nature's choice of metal ion and reaction mechanism and allows for finer control of the enzymatic activity, which is a basis for the design of efficient catalysts for the oxygen reduction reaction in fuel cells.

Original languageEnglish (US)
Pages (from-to)12209-12218
Number of pages10
JournalJournal of the American Chemical Society
Volume139
Issue number35
DOIs
StatePublished - Sep 6 2017

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Binding sites
Manganese
Cobalt
Heme
Oxidation-Reduction
Oxidoreductases
Metals
Binding Sites
Metal ions
Copper
Oxygen
Reactive Oxygen Species
Ions
Myoglobin
Fuel cells
Iron
Enzymes
Derivatives
Proteins
Catalysts

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Manganese and Cobalt in the Nonheme-Metal-Binding Site of a Biosynthetic Model of Heme-Copper Oxidase Superfamily Confer Oxidase Activity through Redox-Inactive Mechanism. / Reed, Julian H.; Shi, Yelu; Zhu, Qianhong; Chakraborty, Saumen; Mirts, Evan N.; Petrik, Igor D.; Bhagi-Damodaran, Ambika; Ross, Matthew; Moenne-Loccoz, Pierre; Zhang, Yong; Lu, Yi.

In: Journal of the American Chemical Society, Vol. 139, No. 35, 06.09.2017, p. 12209-12218.

Research output: Contribution to journalArticle

Reed, Julian H. ; Shi, Yelu ; Zhu, Qianhong ; Chakraborty, Saumen ; Mirts, Evan N. ; Petrik, Igor D. ; Bhagi-Damodaran, Ambika ; Ross, Matthew ; Moenne-Loccoz, Pierre ; Zhang, Yong ; Lu, Yi. / Manganese and Cobalt in the Nonheme-Metal-Binding Site of a Biosynthetic Model of Heme-Copper Oxidase Superfamily Confer Oxidase Activity through Redox-Inactive Mechanism. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 35. pp. 12209-12218.
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AU - Shi, Yelu

AU - Zhu, Qianhong

AU - Chakraborty, Saumen

AU - Mirts, Evan N.

AU - Petrik, Igor D.

AU - Bhagi-Damodaran, Ambika

AU - Ross, Matthew

AU - Moenne-Loccoz, Pierre

AU - Zhang, Yong

AU - Lu, Yi

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AB - The presence of a nonheme metal, such as copper and iron, in the heme-copper oxidase (HCO) superfamily is critical to the enzymatic activity of reducing O2 to H2O, but the exact mechanism the nonheme metal ion uses to confer and fine-tune the activity remains to be understood. We herein report that manganese and cobalt can bind to the same nonheme site and confer HCO activity in a heme-nonheme biosynthetic model in myoglobin. While the initial rates of O2 reduction by the Mn, Fe, and Co derivatives are similar, the percentages of reactive oxygen species (ROS) formation are 7%, 4%, and 1% and the total turnovers are 5.1 ± 1.1, 13.4 ± 0.7, and 82.5 ± 2.5, respectively. These results correlate with the trends of nonheme-metal-binding dissociation constants (35, 22, and 9 μM) closely, suggesting that tighter metal binding can prevent ROS release from the active site, lessen damage to the protein, and produce higher total turnover numbers. Detailed spectroscopic, electrochemical, and computational studies found no evidence of redox cycling of manganese or cobalt in the enzymatic reactions and suggest that structural and electronic effects related to the presence of different nonheme metals lead to the observed differences in reactivity. This study of the roles of nonheme metal ions beyond the Cu and Fe found in native enzymes has provided deeper insights into nature's choice of metal ion and reaction mechanism and allows for finer control of the enzymatic activity, which is a basis for the design of efficient catalysts for the oxygen reduction reaction in fuel cells.

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