The crystal structure of seabream antiquitin reveals the structural basis of its substrate specificity

Wai Kwan Tang; Kam Bo Wong; Yuk Man Lam; Sun Shin Cha; Christopher H.K. Cheng; Wing Ping Fong

doi:10.1016/j.febslet.2008.07.059

The crystal structure of seabream antiquitin reveals the structural basis of its substrate specificity

Wai Kwan Tang, Kam Bo Wong, Yuk Man Lam, Sun Shin Cha, Christopher H.K. Cheng, Wing Ping Fong

Chemistry & Nanoscience

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

16 Scopus citations

Abstract

The crystal structure of seabream antiquitin in complex with the cofactor NAD⁺ was solved at 2.8 Å resolution. The mouth of the substrate-binding pocket is guarded by two conserved residues, Glu120 and Arg300. To test the role of these two residues, we have prepared the two mutants E120A and R300A. Our model and kinetics data suggest that antiquitin's specificity towards the substrate α-aminoadipic semialdehyde is contributed mainly by Glu120 which interacts with the α-amino group of the substrate. On the other hand, Arg300 does not have any specific interaction with the α-carboxylate group of the substrate, but is important in maintaining the active site conformation.

Original language	English
Pages (from-to)	3090-3096
Number of pages	7
Journal	FEBS Letters
Volume	582
Issue number	20
DOIs	https://doi.org/10.1016/j.febslet.2008.07.059
State	Published - 3 Sep 2008

Keywords

ALDH7
Antiquitin
Pyridoxine-dependent epilepsy
Site-directed mutagenesis
X-ray crystallography
α-Aminoadipic semialdehyde

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10.1016/j.febslet.2008.07.059

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title = "The crystal structure of seabream antiquitin reveals the structural basis of its substrate specificity",

abstract = "The crystal structure of seabream antiquitin in complex with the cofactor NAD+ was solved at 2.8 {\AA} resolution. The mouth of the substrate-binding pocket is guarded by two conserved residues, Glu120 and Arg300. To test the role of these two residues, we have prepared the two mutants E120A and R300A. Our model and kinetics data suggest that antiquitin's specificity towards the substrate α-aminoadipic semialdehyde is contributed mainly by Glu120 which interacts with the α-amino group of the substrate. On the other hand, Arg300 does not have any specific interaction with the α-carboxylate group of the substrate, but is important in maintaining the active site conformation.",

keywords = "ALDH7, Antiquitin, Pyridoxine-dependent epilepsy, Site-directed mutagenesis, X-ray crystallography, α-Aminoadipic semialdehyde",

author = "Tang, {Wai Kwan} and Wong, {Kam Bo} and Lam, {Yuk Man} and Cha, {Sun Shin} and Cheng, {Christopher H.K.} and Fong, {Wing Ping}",

note = "Funding Information: This work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (Project No. 464407). Work performed at KORDI was supported by the Marine & Extreme Genome Research Center Program, Ministry of Land, Transport, and Maritime Affairs, Republic of Korea.",

year = "2008",

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doi = "10.1016/j.febslet.2008.07.059",

language = "English",

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T1 - The crystal structure of seabream antiquitin reveals the structural basis of its substrate specificity

AU - Tang, Wai Kwan

AU - Wong, Kam Bo

AU - Lam, Yuk Man

AU - Cha, Sun Shin

AU - Cheng, Christopher H.K.

AU - Fong, Wing Ping

N1 - Funding Information: This work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region (Project No. 464407). Work performed at KORDI was supported by the Marine & Extreme Genome Research Center Program, Ministry of Land, Transport, and Maritime Affairs, Republic of Korea.

PY - 2008/9/3

Y1 - 2008/9/3

N2 - The crystal structure of seabream antiquitin in complex with the cofactor NAD+ was solved at 2.8 Å resolution. The mouth of the substrate-binding pocket is guarded by two conserved residues, Glu120 and Arg300. To test the role of these two residues, we have prepared the two mutants E120A and R300A. Our model and kinetics data suggest that antiquitin's specificity towards the substrate α-aminoadipic semialdehyde is contributed mainly by Glu120 which interacts with the α-amino group of the substrate. On the other hand, Arg300 does not have any specific interaction with the α-carboxylate group of the substrate, but is important in maintaining the active site conformation.

AB - The crystal structure of seabream antiquitin in complex with the cofactor NAD+ was solved at 2.8 Å resolution. The mouth of the substrate-binding pocket is guarded by two conserved residues, Glu120 and Arg300. To test the role of these two residues, we have prepared the two mutants E120A and R300A. Our model and kinetics data suggest that antiquitin's specificity towards the substrate α-aminoadipic semialdehyde is contributed mainly by Glu120 which interacts with the α-amino group of the substrate. On the other hand, Arg300 does not have any specific interaction with the α-carboxylate group of the substrate, but is important in maintaining the active site conformation.

KW - ALDH7

KW - Antiquitin

KW - Pyridoxine-dependent epilepsy

KW - Site-directed mutagenesis

KW - X-ray crystallography

KW - α-Aminoadipic semialdehyde

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U2 - 10.1016/j.febslet.2008.07.059

DO - 10.1016/j.febslet.2008.07.059

M3 - Article

C2 - 18694748

AN - SCOPUS:49649114051

SN - 0014-5793

VL - 582

SP - 3090

EP - 3096

JO - FEBS Letters

JF - FEBS Letters

IS - 20

ER -

The crystal structure of seabream antiquitin reveals the structural basis of its substrate specificity

Abstract

Keywords

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