An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzymeCitation formats

  • External authors:
  • Mary Ortmayer
  • Pierre Lafite
  • Binuraj R K Menon
  • Tewes Tralau
  • Karl Fisher
  • Lukas Denkhaus
  • Steve Rigby

Standard

An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme. / Ortmayer, Mary; Lafite, Pierre; Menon, Binuraj R K et al.

In: Nature, Vol. 539, No. 7630, 16.11.2016, p. 593-597.

Research output: Contribution to journalArticlepeer-review

Harvard

Ortmayer, M, Lafite, P, Menon, BRK, Tralau, T, Fisher, K, Denkhaus, L, Scrutton, N, Rigby, S, Munro, A, Hay, S & Leys, D 2016, 'An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme', Nature, vol. 539, no. 7630, pp. 593-597. https://doi.org/10.1038/nature20159

APA

Ortmayer, M., Lafite, P., Menon, B. R. K., Tralau, T., Fisher, K., Denkhaus, L., Scrutton, N., Rigby, S., Munro, A., Hay, S., & Leys, D. (2016). An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme. Nature, 539(7630), 593-597. https://doi.org/10.1038/nature20159

Vancouver

Ortmayer M, Lafite P, Menon BRK, Tralau T, Fisher K, Denkhaus L et al. An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme. Nature. 2016 Nov 16;539(7630):593-597. https://doi.org/10.1038/nature20159

Author

Ortmayer, Mary ; Lafite, Pierre ; Menon, Binuraj R K et al. / An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme. In: Nature. 2016 ; Vol. 539, No. 7630. pp. 593-597.

Bibtex

@article{6703550eed234f44a0b8cf98a85a6f7e,
title = "An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme",
abstract = "The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases. The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine. The structure of the α subunit reveals that it is a haem-binding PAS domain, similar in structure to PAS gas sensors. The dimethylamine substrate forms part of a highly polarized oxygen-binding site, and directly assists oxygen activation by acting as both an electron and proton donor. Our data reveal that the ubiquitous PAS domain can make the transition from sensor to enzyme, suggesting that the PAS scaffold can support the development of artificial enzymes.",
author = "Mary Ortmayer and Pierre Lafite and Menon, {Binuraj R K} and Tewes Tralau and Karl Fisher and Lukas Denkhaus and Nigel Scrutton and Steve Rigby and Andrew Munro and Sam Hay and David Leys",
year = "2016",
month = nov,
day = "16",
doi = "10.1038/nature20159",
language = "English",
volume = "539",
pages = "593--597",
journal = "Nature: international weekly journal of science",
issn = "0028-0836",
publisher = "Springer Nature",
number = "7630",

}

RIS

TY - JOUR

T1 - An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme

AU - Ortmayer, Mary

AU - Lafite, Pierre

AU - Menon, Binuraj R K

AU - Tralau, Tewes

AU - Fisher, Karl

AU - Denkhaus, Lukas

AU - Scrutton, Nigel

AU - Rigby, Steve

AU - Munro, Andrew

AU - Hay, Sam

AU - Leys, David

PY - 2016/11/16

Y1 - 2016/11/16

N2 - The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases. The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine. The structure of the α subunit reveals that it is a haem-binding PAS domain, similar in structure to PAS gas sensors. The dimethylamine substrate forms part of a highly polarized oxygen-binding site, and directly assists oxygen activation by acting as both an electron and proton donor. Our data reveal that the ubiquitous PAS domain can make the transition from sensor to enzyme, suggesting that the PAS scaffold can support the development of artificial enzymes.

AB - The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases. The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine. The structure of the α subunit reveals that it is a haem-binding PAS domain, similar in structure to PAS gas sensors. The dimethylamine substrate forms part of a highly polarized oxygen-binding site, and directly assists oxygen activation by acting as both an electron and proton donor. Our data reveal that the ubiquitous PAS domain can make the transition from sensor to enzyme, suggesting that the PAS scaffold can support the development of artificial enzymes.

U2 - 10.1038/nature20159

DO - 10.1038/nature20159

M3 - Article

C2 - 27851736

VL - 539

SP - 593

EP - 597

JO - Nature: international weekly journal of science

JF - Nature: international weekly journal of science

SN - 0028-0836

IS - 7630

ER -