2dfv

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2dfv, resolution 2.05Å

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Hyperthermophilic threonine dehydrogenase from Pyrococcus horikoshii

Overview

l-Threonine dehydrogenase (TDH) is an enzyme that catalyzes the oxidation, of l-threonine to 2-amino-3-ketobutyrate. We solved the first crystal, structure of a medium chain l-threonine dehydrogenase from a, hyperthermophilic archaeon, Pyrococcus horikoshii (PhTDH), by the single, wavelength anomalous diffraction method using a, selenomethionine-substituted enzyme. This recombinant PhTDH is a, homo-tetramer in solution. Three monomers of PhTDHs were located in the, crystallographic asymmetric unit, however, the crystal structure exhibits, a homo-tetramer structure with crystallographic and non-crystallographic, 222 symmetry in the cell. Despite the low level of sequence identity to a, medium-chain NAD(H)-dependent alcohol dehydrogenase (ADH) and the, different substrate specificity, the overall folds of the PhTDH monomer, and tetramer are similar to those of the other ADH. Each subunit is, composed of two domains: a nicotinamide cofactor (NAD(H))-binding domain, and a catalytic domain. The NAD(H)-binding domain contains the alpha/beta, Rossmann fold motif, characteristic of the NAD(H)-binding protein. One, molecule of PhTDH contains one zinc ion playing a structural role. This, metal ion exhibits coordination with four cysteine ligands and some of the, ligands are conserved throughout the structural zinc-containing ADHs and, TDHs. However, the catalytic zinc ion that is coordinated at the bottom of, the cleft in the case of ADH was not observed in the crystal of PhTDH., There is a significant difference in the orientation of the catalytic, domain relative to the coenzyme-binding domain that results in a larger, interdomain cleft.

About this Structure

2DFV is a Single protein structure of sequence from Pyrococcus horikoshii with ZN, SO4 and NAD as ligands. Active as L-threonine 3-dehydrogenase, with EC number 1.1.1.103 Full crystallographic information is available from OCA.

Reference

The First Crystal Structure of l-Threonine Dehydrogenase., Ishikawa K, Higashi N, Nakamura T, Matsuura T, Nakagawa A, J Mol Biol. 2007 Feb 23;366(3):857-67. Epub 2006 Nov 21. PMID:17188300

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