The 2.9A resolution crystal structure of malate dehydrogenase from Archaeoglobus fulgidus: mechanisms of oligomerisation and thermal stabilisation

The crystal structure of malate dehydrogenase from the hyperthermophilic archaeon Archeoglobus fulgidus, in complex with its cofactor NAD, was solved at 2.9A resolution. The crystal structure shows a compact homodimer with one coenzyme bound per subunit. The substrate binding site is occupied by a s...

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Bibliographic Details
Published in:Journal of molecular biology 2004-01, Vol.335 (1), p.343-356
Main Authors: Irimia, Adriana, Vellieux, Frédéric M D, Madern, Dominique, Zaccaï, Giuseppe, Karshikoff, Andrey, Tibbelin, Gudrun, Ladenstein, Rudolf, Lien, Torleiv, Birkeland, Nils Kåre
Format: Article
Language:English
Subjects:
Archaeoglobus fulgidus - enzymology
Archeoglobus fulgidus
Crystallography, X-Ray
Dimerization
Enzyme Stability
Malate Dehydrogenase - chemistry
Molecular Structure
NAD - chemistry
Protein Conformation
Structural Homology, Protein
Temperature
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Summary:The crystal structure of malate dehydrogenase from the hyperthermophilic archaeon Archeoglobus fulgidus, in complex with its cofactor NAD, was solved at 2.9A resolution. The crystal structure shows a compact homodimer with one coenzyme bound per subunit. The substrate binding site is occupied by a sulphate ion. In order to gain insight into adaptation mechanisms, which allow the protein to be stable and active at high temperatures, the 3D structure was compared to those of several thermostable and hyperthermostable homologues, and to halophilic malate dehydrogenase. The hyperthermostable A. fulgidus MalDH protein displays a reduction of the solvent-exposed surface, an optimised compact hydrophobic core, a high number of hydrogen bonds, and includes a large number of ion pairs at the protein surface. These features occur concomitantly with a reduced number of residues in the protein subunit, due to several deletions in loop regions. The loops are further stiffened by ion pair links with secondary structure elements. A. fulgidus malate dehydrogenase is the only dimeric protein known to date that belongs to the [LDH-like] MalDH family. All the other known members of this family are homo-tetramers. The crystal structures revealed that the association of the dimers to form tetramers is prevented by several deletions, taking place at the level of two loops that are known to be essential for the tetramerisation process within the LDH and [LDH-like] MalDH enzymes.
ISSN:0022-2836
DOI:10.1016/j.jmb.2003.10.054