Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase. / Lim, Yean J.; Foo, Timothy C.; Yeung, Amanda W. S.; Tu, Xiaofan; Ma, Yuanqing; Hawkins, Clare L.; Witting, Paul K.; Jameson, Guy N. L.; Terentis, Andrew C.; Thomas, Shane R.

In: Biochemistry, Vol. 58, No. 7, 2019, p. 974-986.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lim, YJ, Foo, TC, Yeung, AWS, Tu, X, Ma, Y, Hawkins, CL, Witting, PK, Jameson, GNL, Terentis, AC & Thomas, SR 2019, 'Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase', Biochemistry, vol. 58, no. 7, pp. 974-986. https://doi.org/10.1021/acs.biochem.8b01231

APA

Lim, Y. J., Foo, T. C., Yeung, A. W. S., Tu, X., Ma, Y., Hawkins, C. L., ... Thomas, S. R. (2019). Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase. Biochemistry, 58(7), 974-986. https://doi.org/10.1021/acs.biochem.8b01231

Vancouver

Lim YJ, Foo TC, Yeung AWS, Tu X, Ma Y, Hawkins CL et al. Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase. Biochemistry. 2019;58(7):974-986. https://doi.org/10.1021/acs.biochem.8b01231

Author

Lim, Yean J. ; Foo, Timothy C. ; Yeung, Amanda W. S. ; Tu, Xiaofan ; Ma, Yuanqing ; Hawkins, Clare L. ; Witting, Paul K. ; Jameson, Guy N. L. ; Terentis, Andrew C. ; Thomas, Shane R. / Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase. In: Biochemistry. 2019 ; Vol. 58, No. 7. pp. 974-986.

Bibtex

@article{584f555cac234982ba2dc5da3eb03c59,
title = "Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase",
abstract = "The heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of L-tryptophan oxidation along the kynurenine pathway. IDOL is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Here we demonstrate that IDO1 is a mammalian nitrite reductase capable of chemically reducing nitrite to nitric oxide (NO) under hypoxia. Ultraviolet visible absorption and resonance Raman spectroscopy showed that incubation of dithionite-reduced, ferrous-IDO1 protein (Fe IDO1) with nitrite under anaerobic conditions resulted in the time dependent formation of an Fell nitrosyl IDO1 species, which was inhibited by substrate L-tryptophan, dependent on the concentration of nitrite or IDO1, and independent of the concentration of the reductant, dithionite. The bimolecular rate constant for IDO1 nitrite reductase activity was determined as 5.4 M-1 s(-1) (pH 7.4, 23 degrees C), which was comparable to that measured for myoglobin (3.6 M-1 s(-1); pH 7.4, 23 degrees C), an efficient and biologically important mammalian heme-based nitrite reductase. IDO1 nitrite reductase activity was pH-dependent but differed with myoglobin in that it showed a reduced proton dependency at pH >7. Electron paramagnetic resonance studies measuring NO production showed that the conventional IDO1 dioxygenase reducing cofactors, ascorbate and methylene blue, enhanced IDO1's nitrite reductase activity and the time- and IDO1 concentration-dependent release of NO in a manner inhibited by L-tryptophan or the IDO inhibitor 1-methyl-L-tryptophan. These data identify IDO1 as an efficient mammalian nitrite reductase that is capable of generating NO under anaerobic conditions. IDO1's nitrite reductase activity may have important implications for the enzyme's biological actions when expressed within hypoxic tissues",
author = "Lim, {Yean J.} and Foo, {Timothy C.} and Yeung, {Amanda W. S.} and Xiaofan Tu and Yuanqing Ma and Hawkins, {Clare L.} and Witting, {Paul K.} and Jameson, {Guy N. L.} and Terentis, {Andrew C.} and Thomas, {Shane R.}",
year = "2019",
doi = "10.1021/acs.biochem.8b01231",
language = "English",
volume = "58",
pages = "974--986",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "7",

}

RIS

TY - JOUR

T1 - Human Indoleamine 2,3-Dioxygenase 1 Is an Efficient Mammalian Nitrite Reductase

AU - Lim, Yean J.

AU - Foo, Timothy C.

AU - Yeung, Amanda W. S.

AU - Tu, Xiaofan

AU - Ma, Yuanqing

AU - Hawkins, Clare L.

AU - Witting, Paul K.

AU - Jameson, Guy N. L.

AU - Terentis, Andrew C.

AU - Thomas, Shane R.

PY - 2019

Y1 - 2019

N2 - The heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of L-tryptophan oxidation along the kynurenine pathway. IDOL is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Here we demonstrate that IDO1 is a mammalian nitrite reductase capable of chemically reducing nitrite to nitric oxide (NO) under hypoxia. Ultraviolet visible absorption and resonance Raman spectroscopy showed that incubation of dithionite-reduced, ferrous-IDO1 protein (Fe IDO1) with nitrite under anaerobic conditions resulted in the time dependent formation of an Fell nitrosyl IDO1 species, which was inhibited by substrate L-tryptophan, dependent on the concentration of nitrite or IDO1, and independent of the concentration of the reductant, dithionite. The bimolecular rate constant for IDO1 nitrite reductase activity was determined as 5.4 M-1 s(-1) (pH 7.4, 23 degrees C), which was comparable to that measured for myoglobin (3.6 M-1 s(-1); pH 7.4, 23 degrees C), an efficient and biologically important mammalian heme-based nitrite reductase. IDO1 nitrite reductase activity was pH-dependent but differed with myoglobin in that it showed a reduced proton dependency at pH >7. Electron paramagnetic resonance studies measuring NO production showed that the conventional IDO1 dioxygenase reducing cofactors, ascorbate and methylene blue, enhanced IDO1's nitrite reductase activity and the time- and IDO1 concentration-dependent release of NO in a manner inhibited by L-tryptophan or the IDO inhibitor 1-methyl-L-tryptophan. These data identify IDO1 as an efficient mammalian nitrite reductase that is capable of generating NO under anaerobic conditions. IDO1's nitrite reductase activity may have important implications for the enzyme's biological actions when expressed within hypoxic tissues

AB - The heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of L-tryptophan oxidation along the kynurenine pathway. IDOL is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Here we demonstrate that IDO1 is a mammalian nitrite reductase capable of chemically reducing nitrite to nitric oxide (NO) under hypoxia. Ultraviolet visible absorption and resonance Raman spectroscopy showed that incubation of dithionite-reduced, ferrous-IDO1 protein (Fe IDO1) with nitrite under anaerobic conditions resulted in the time dependent formation of an Fell nitrosyl IDO1 species, which was inhibited by substrate L-tryptophan, dependent on the concentration of nitrite or IDO1, and independent of the concentration of the reductant, dithionite. The bimolecular rate constant for IDO1 nitrite reductase activity was determined as 5.4 M-1 s(-1) (pH 7.4, 23 degrees C), which was comparable to that measured for myoglobin (3.6 M-1 s(-1); pH 7.4, 23 degrees C), an efficient and biologically important mammalian heme-based nitrite reductase. IDO1 nitrite reductase activity was pH-dependent but differed with myoglobin in that it showed a reduced proton dependency at pH >7. Electron paramagnetic resonance studies measuring NO production showed that the conventional IDO1 dioxygenase reducing cofactors, ascorbate and methylene blue, enhanced IDO1's nitrite reductase activity and the time- and IDO1 concentration-dependent release of NO in a manner inhibited by L-tryptophan or the IDO inhibitor 1-methyl-L-tryptophan. These data identify IDO1 as an efficient mammalian nitrite reductase that is capable of generating NO under anaerobic conditions. IDO1's nitrite reductase activity may have important implications for the enzyme's biological actions when expressed within hypoxic tissues

U2 - 10.1021/acs.biochem.8b01231

DO - 10.1021/acs.biochem.8b01231

M3 - Journal article

C2 - 30585477

VL - 58

SP - 974

EP - 986

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 7

ER -

ID: 229270149