Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase

Jaswir Basran; Elizabeth S. Booth; Laura P. Campbell; Sarah J. Thackray; Mehul H. Jesani; Jonathan Clayden; Peter C.E. Moody; Christopher G. Mowat; Hanna Kwon; Emma L. Raven

doi:10.1016/j.jinorgbio.2021.111604

Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase

Jaswir Basran, Elizabeth S. Booth, Laura P. Campbell, Sarah J. Thackray, Mehul H. Jesani, Jonathan Clayden, Peter C.E. Moody, Christopher G. Mowat, Hanna Kwon^*, Emma L. Raven

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes – tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) – leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with L-kynurenine, the hydrolysed product of NFK. L-kynurenine is bound at the active site in a similar location to the substrate (L-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the L-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.

Original language	English
Article number	111604
Journal	Journal of Inorganic Biochemistry
Volume	225
Early online date	16 Sept 2021
DOIs	https://doi.org/10.1016/j.jinorgbio.2021.111604
Publication status	E-pub ahead of print - 16 Sept 2021

Keywords / Materials (for Non-textual outputs)

Heme
Kynurenine
Tryptophan 2,3-dioxygenase

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10.1016/j.jinorgbio.2021.111604

20211026_Mowat_AAMAccepted author manuscript, 1.79 MBLicence: CC BY-NC-ND

https://www.sciencedirect.com/science/article/pii/S0162013421002518

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@article{72b38e39236c4c3ea358e4daa9829c9e,

title = "Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase",

abstract = "The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes – tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) – leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with L-kynurenine, the hydrolysed product of NFK. L-kynurenine is bound at the active site in a similar location to the substrate (L-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the L-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.",

keywords = "Heme, Kynurenine, Tryptophan 2,3-dioxygenase",

author = "Jaswir Basran and Booth, \{Elizabeth S.\} and Campbell, \{Laura P.\} and Thackray, \{Sarah J.\} and Jesani, \{Mehul H.\} and Jonathan Clayden and Moody, \{Peter C.E.\} and Mowat, \{Christopher G.\} and Hanna Kwon and Raven, \{Emma L.\}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = sep,

day = "16",

doi = "10.1016/j.jinorgbio.2021.111604",

language = "English",

volume = "225",

journal = "Journal of Inorganic Biochemistry",

issn = "0162-0134",

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TY - JOUR

T1 - Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase

AU - Basran, Jaswir

AU - Booth, Elizabeth S.

AU - Campbell, Laura P.

AU - Thackray, Sarah J.

AU - Jesani, Mehul H.

AU - Clayden, Jonathan

AU - Moody, Peter C.E.

AU - Mowat, Christopher G.

AU - Kwon, Hanna

AU - Raven, Emma L.

PY - 2021/9/16

Y1 - 2021/9/16

N2 - The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes – tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) – leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with L-kynurenine, the hydrolysed product of NFK. L-kynurenine is bound at the active site in a similar location to the substrate (L-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the L-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.

AB - The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes – tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) – leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with L-kynurenine, the hydrolysed product of NFK. L-kynurenine is bound at the active site in a similar location to the substrate (L-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the L-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.

KW - Heme

KW - Kynurenine

KW - Tryptophan 2,3-dioxygenase

U2 - 10.1016/j.jinorgbio.2021.111604

DO - 10.1016/j.jinorgbio.2021.111604

M3 - Article

AN - SCOPUS:85115603005

SN - 0162-0134

VL - 225

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

M1 - 111604

ER -

Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase

Abstract

Keywords / Materials (for Non-textual outputs)

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