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 P Clayden; Peter C.E. Moody; Christopher G. Mowat; Emma Raven; Hanna Kwon

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 P Clayden, Peter C.E. Moody, Christopher G. Mowat, Emma Raven^*, Hanna Kwon^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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
Number of pages	6
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	Published - 1 Dec 2021

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© 2021

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BCS and TECS CDTs

Keywords

Heme
Tryptophan 2,3-dioxygenase
IDOindoleamine 2,3-dioxygenase

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@article{9422f029535b4173a239f6b181a2f19c,

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, Tryptophan 2,3-dioxygenase, IDOindoleamine 2,3-dioxygenase",

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

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

year = "2021",

month = dec,

day = "1",

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

language = "English",

volume = "225",

journal = "Journal of Inorganic Biochemistry",

issn = "0162-0134",

publisher = "Elsevier Inc.",

}

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 P

AU - Moody, Peter C.E.

AU - Mowat, Christopher G.

AU - Raven, Emma

AU - Kwon, Hanna

PY - 2021/12/1

Y1 - 2021/12/1

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 - Tryptophan 2,3-dioxygenase

KW - IDOindoleamine 2,3-dioxygenase

U2 - 10.1016/j.jinorgbio.2021.111604

DO - 10.1016/j.jinorgbio.2021.111604

M3 - Article (Academic Journal)

C2 - 34571402

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

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