9IBE

D-2-hydroxyacid dehydrogenase (D2HDH) from Haloferax mediterranei in complex with potassium, 2-ketohexanoic acid, NADP+ and chloride

Summary for 9IBE

• Entry DOI: 10.2210/pdb9ibe/pdb
• Related: 5mh5 5mh6 5mha 8qza 8qzb
• Descriptor: D-2-hydroxyacid dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-Ketohexanoic acid, ... (7 entities in total)
• Functional Keywords: halophile, halophilic adaptation, potassium binding, complex, substrate specificity, oxidoreductase
• Biological source: Haloferax mediterranei
• Total number of polymer chains: 4
• Total formula weight: 138334.33

Authors

Baker, P.J.,Barrett, J.R.,Dakhil, A.A.A.B.,Domenech, J.,Bisson, C.,Pramanpol, N.,Ferrer, J.,Rice, D.W. (deposition date: 2025-02-12, release date: 2025-08-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.26 Å)