8QZA

D-2-hydroxyacid dehydrogenase (D2-HDH) from Haloferax mediterranei apo-enzyme (2.25 A resolution)

8QZA の概要

• エントリーDOI: 10.2210/pdb8qza/pdb
• 分子名称: D-2-hydroxyacid dehydrogenase, MAGNESIUM ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: halophilic adaptation domain closure mechanism, oxidoreductase
• 由来する生物種: Haloferax mediterranei
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66903.49

構造登録者

Baker, P.J.,Barrett, J.R.,Dakhil, A.A.A.B.,Domenech, J.,Bisson, C.,Pramanpol, N.,Sedelnikova, S.E.,Ferrer, J.,Rice, D.W. (登録日: 2023-10-26, 公開日: 2025-08-06, 最終更新日: 2025-08-20)

主引用文献

Domenech, J.,Pramanpol, N.,Bisson, C.,Sedelnikova, S.E.,Barrett, J.R.,Dakhil, A.A.A.B.,Mykhaylyk, V.,Abdelhameed, A.S.,Harding, S.E.,Rice, D.W.,Baker, P.J.,Ferrer, J.
Potassium binding by carbonyl clusters, halophilic adaptation and catalysis of Haloferax mediterranei D-2-hydroxyacid dehydrogenase.
Commun Biol, 8:1170-1170, 2025

PubMed Abstract: Enzymes from salt-in halophiles are stable in conditions of low water activity with applications in chiral synthesis requiring organic solvents, yet the origins of such stability remains poorly understood. Here we describe the molecular basis of the reaction mechanism and dual NADH/NADPH-specificity of D2HDH, a 2-hydroxyacid dehydrogenase from the extreme halophile Haloferax mediterranei, an organism whose proteins have to remain active in high intracellular concentrations of KCl. Halophilic adaptations of D2HDH include the expected acidic surface and a reduction in hydrophobic surface resulting from a lower lysine content. Structure determination of crystals of D2HDH grown with KCl showed that bound K ions were coordinated predominantly by clusters of main chain protein carbonyl ligands, with no involvement of the numerous exposed surface carboxyls. Structural comparisons identified similar sites in other halophilic proteins suggesting that the generic use of carbonyl clusters to coordinate K ions may also contribute in a carboxylate-independent way to the stabilisation of the folded state of the protein in its high salt environment.

PubMed: 40770045
DOI: 10.1038/s42003-025-08587-7

実験手法

X-RAY DIFFRACTION (2.252 Å)