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Structure and function of the l-threonine dehydrogenase (TkTDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis

Structure and function of the l-threonine dehydrogenase (TkTDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis
Structure and function of the l-threonine dehydrogenase (TkTDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis
The X-ray structure of the holo-form of l-threonine dehydrogenase (TDH) from Thermococcus kodakaraensis (TkTDH) has been determined at 2.4 Å resolution. TDH catalyses the NAD+-dependent oxidation of l-threonine to 2-amino-3-ketobutyrate, and is one of the first enzymes in this family to be solved by X-ray crystallography. The enzyme is a homo-tetramer, each monomer consisting of 350 amino acids that form two domains; a catalytic domain and a nicotinamide co-factor (NAD+)-binding domain, which contains an ?/? Rossmann fold motif. An extended twelve-stranded ?-sheet is formed by the association of pairs of monomers in the tetramer. TkTDH shows strong overall structural similarity to TDHs from thermophiles and alcohol dehydrogenases (ADH) from lower life forms, despite low sequence homology, exhibiting the same overall fold of the monomer and assembly of the tetramer. The structure reveals the binding site of the essential co-factor NAD+ which is present in all subunits. Docking studies suggest a mode of interaction of TDH with 2-amino-3-ketobutyrate CoA ligase, the subsequent enzyme in the pathway for conversion of threonine to glycine. TDH is known to form a stable functional complex with 2-amino-3-ketobutyrate ligase, most probably to shield an unstable intermediate.
threonine dehydrogenase, x-ray crystallography, docking, multi-enzyme complex, channelling
1047-8477
294-304
Bowyer, A.
bfa8d898-7590-4536-a9ce-1a626a46b15c
Mikolajek, H.
c394c255-9248-4217-ace9-4a0382bfc0c5
Stuart, J.W.
59789b2c-ab7f-45dd-8cdf-b73f03723ead
Wood, S.P.
430faabf-7f5c-4cf6-9bcc-5955f5e09566
Jamil, F.
a3660507-e703-48a7-99d8-b4a101645e18
Rashid, N.
ca94ad4e-c02a-4662-84d2-c28a648793be
Akhtar, M.
a4174002-a6bd-4678-8e63-4cbe607a672d
Cooper, J.B.
d9f0f6a8-1260-48fc-aa5c-3dbc650e3ec0
Bowyer, A.
bfa8d898-7590-4536-a9ce-1a626a46b15c
Mikolajek, H.
c394c255-9248-4217-ace9-4a0382bfc0c5
Stuart, J.W.
59789b2c-ab7f-45dd-8cdf-b73f03723ead
Wood, S.P.
430faabf-7f5c-4cf6-9bcc-5955f5e09566
Jamil, F.
a3660507-e703-48a7-99d8-b4a101645e18
Rashid, N.
ca94ad4e-c02a-4662-84d2-c28a648793be
Akhtar, M.
a4174002-a6bd-4678-8e63-4cbe607a672d
Cooper, J.B.
d9f0f6a8-1260-48fc-aa5c-3dbc650e3ec0

Bowyer, A., Mikolajek, H., Stuart, J.W., Wood, S.P., Jamil, F., Rashid, N., Akhtar, M. and Cooper, J.B. (2009) Structure and function of the l-threonine dehydrogenase (TkTDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis. Journal of Structural Biology, 168 (2), 294-304. (doi:10.1016/j.jsb.2009.07.011). (PMID:19616102)

Record type: Article

Abstract

The X-ray structure of the holo-form of l-threonine dehydrogenase (TDH) from Thermococcus kodakaraensis (TkTDH) has been determined at 2.4 Å resolution. TDH catalyses the NAD+-dependent oxidation of l-threonine to 2-amino-3-ketobutyrate, and is one of the first enzymes in this family to be solved by X-ray crystallography. The enzyme is a homo-tetramer, each monomer consisting of 350 amino acids that form two domains; a catalytic domain and a nicotinamide co-factor (NAD+)-binding domain, which contains an ?/? Rossmann fold motif. An extended twelve-stranded ?-sheet is formed by the association of pairs of monomers in the tetramer. TkTDH shows strong overall structural similarity to TDHs from thermophiles and alcohol dehydrogenases (ADH) from lower life forms, despite low sequence homology, exhibiting the same overall fold of the monomer and assembly of the tetramer. The structure reveals the binding site of the essential co-factor NAD+ which is present in all subunits. Docking studies suggest a mode of interaction of TDH with 2-amino-3-ketobutyrate CoA ligase, the subsequent enzyme in the pathway for conversion of threonine to glycine. TDH is known to form a stable functional complex with 2-amino-3-ketobutyrate ligase, most probably to shield an unstable intermediate.

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More information

e-pub ahead of print date: 16 July 2009
Published date: November 2009
Keywords: threonine dehydrogenase, x-ray crystallography, docking, multi-enzyme complex, channelling
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 337111
URI: https://eprints.soton.ac.uk/id/eprint/337111
ISSN: 1047-8477
PURE UUID: 0994505e-b8d3-4796-8fb8-7c32c6284521
ORCID for H. Mikolajek: ORCID iD orcid.org/0000-0003-0776-9974

Catalogue record

Date deposited: 18 Apr 2012 11:17
Last modified: 16 Jul 2019 22:07

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