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Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases

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Abstract
Isomerization reactions are fundamental in biology. Lactate racemase, which isomerizes L- and D-lactate, is composed of the LarA protein and a nickel-containing cofactor, the nickel-pincer nucleotide (NPN). In this study, we show that LarA is part of a superfamily containing many different enzymes. We overexpressed and purified 13 lactate racemase homologs, incorporated the NPN cofactor, and assayed the isomerization of different substrates guided by gene context analysis. We discovered two malate racemases, one phenyllactate racemase, one α-hydroxyglutarate racemase, two D-gluconate 2-epimerases, and one short-chain aliphatic α-hydroxyacid racemase among the tested enzymes. We solved the structure of a malate racemase apoprotein and used it, along with the previously described structures of lactate racemase holoprotein and D-gluconate epimerase apoprotein, to identify key residues involved in substrate binding. This study demonstrates that the NPN cofactor is used by a diverse superfamily of α-hydroxyacid racemases and epimerases, widely expanding the scope of NPN-dependent enzymes.
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Multidisciplinary

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MLA
Desguin, Benoît, et al. “Uncovering a Superfamily of Nickel-Dependent Hydroxyacid Racemases and Epimerases.” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020, doi:10.1038/s41598-020-74802-6.
APA
Desguin, B., Urdiain-Arraiza, J., Da Costa, M., Fellner, M., Hu, J., Hausinger, R. P., … Soumillion, P. (2020). Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases. SCIENTIFIC REPORTS, 10(1). https://doi.org/10.1038/s41598-020-74802-6
Chicago author-date
Desguin, Benoît, Julian Urdiain-Arraiza, Matthieu Da Costa, Matthias Fellner, Jian Hu, Robert P. Hausinger, Tom Desmet, Pascal Hols, and Patrice Soumillion. 2020. “Uncovering a Superfamily of Nickel-Dependent Hydroxyacid Racemases and Epimerases.” SCIENTIFIC REPORTS 10 (1). https://doi.org/10.1038/s41598-020-74802-6.
Chicago author-date (all authors)
Desguin, Benoît, Julian Urdiain-Arraiza, Matthieu Da Costa, Matthias Fellner, Jian Hu, Robert P. Hausinger, Tom Desmet, Pascal Hols, and Patrice Soumillion. 2020. “Uncovering a Superfamily of Nickel-Dependent Hydroxyacid Racemases and Epimerases.” SCIENTIFIC REPORTS 10 (1). doi:10.1038/s41598-020-74802-6.
Vancouver
1.
Desguin B, Urdiain-Arraiza J, Da Costa M, Fellner M, Hu J, Hausinger RP, et al. Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases. SCIENTIFIC REPORTS. 2020;10(1).
IEEE
[1]
B. Desguin et al., “Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases,” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020.
@article{8693378,
  abstract     = {{Isomerization reactions are fundamental in biology. Lactate racemase, which isomerizes L- and D-lactate, is composed of the LarA protein and a nickel-containing cofactor, the nickel-pincer nucleotide (NPN). In this study, we show that LarA is part of a superfamily containing many different enzymes. We overexpressed and purified 13 lactate racemase homologs, incorporated the NPN cofactor, and assayed the isomerization of different substrates guided by gene context analysis. We discovered two malate racemases, one phenyllactate racemase, one α-hydroxyglutarate racemase, two D-gluconate 2-epimerases, and one short-chain aliphatic α-hydroxyacid racemase among the tested enzymes. We solved the structure of a malate racemase apoprotein and used it, along with the previously described structures of lactate racemase holoprotein and D-gluconate epimerase apoprotein, to identify key residues involved in substrate binding. This study demonstrates that the NPN cofactor is used by a diverse superfamily of α-hydroxyacid racemases and epimerases, widely expanding the scope of NPN-dependent enzymes.}},
  articleno    = {{18123}},
  author       = {{Desguin, Benoît and Urdiain-Arraiza, Julian and Da Costa, Matthieu and Fellner, Matthias and Hu, Jian and Hausinger, Robert P. and Desmet, Tom and Hols, Pascal and Soumillion, Patrice}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{Multidisciplinary}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{11}},
  title        = {{Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases}},
  url          = {{http://doi.org/10.1038/s41598-020-74802-6}},
  volume       = {{10}},
  year         = {{2020}},
}

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