Enzyme - Homoserine dehydrogenase

Alternative Name(s)

There are no alternative names for this Enzyme

Catalytic Activity

L-homoserine + NAD(+) = H(+) + L-aspartate 4-semialdehyde + NADH


There are no Cofactors for this Enzyme

Reaction Mechanism

    Homoserine dehydrogenase belongs to the oxioreductase class of enzymes, although the residues implicated in catalysis are quite different from other enzymes within the class. It is involved in the NAD(P)H dependent reduction of L-aspartate semi-aldehyde to L homoserine, a pathway not found within the animal kingdom. The enzyme has therefore been targeted for the development of antimycotic drugs.

    The NAD(P)H dependent reduction of L aspartate semi-aldehyde proceeds via hydride transfer. The hydride donating NAD(P)H cofactor is bound in the Rossmann fold, where enzyme-cofactor hydrogen bond interactions exist between cofactor phosphate moieties and sugar hydroxyl groups and the enzyme amide back bone groups. The amino substrate is thought to bind predominantly in the aldehyde rather than the hydrate form through hydrogen bond interactions with Asp 214, Glu 208, and a water molecule (460). The catalytic Lys 223 donates a proton to the developing alkoxide tetrahedral intermediate during hydride transfer. Asp 219 is key in positioning the catalytic residue, while the N terminal helix alpha J is important in stabilising the developing negative charge on the substrate carbonyl.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Asp P31116 219 1ebf 218
    Lys P31116 223 1ebf 222

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Bacillus subtilis 0.031 L-homoserine pH 9.0, 25°C, recombinant enzyme
    Glycine max 0.039 L-homoserine cosubstrate NADP+, pH 8.0, 25°C
    Thermus thermophilus 6.2 NAD+ pH 9.5, 50°C, recombinant enzyme
    Pyrococcus horikoshii 89.1 NADP+ pH 9.0, 50°C, recombinant mutant R40A
  • Temperature
    Organism Temperature Range Comment
    Thermophilic bacterium 20 - 70 no activity at 80°C
    Bacillus subtilis 25 - 50 45% of maximal activity at 25°C and 50°C, maximal activity at 35-40°C, 75% at 45°C, 65% at 35°C, profile overview
    Thermotoga maritima 50 - 80 over 30% of maximal activity within this range, profile overview
  • pH
    Organism pH Range Comment
    Thermotoga maritima 6.5 - 11 over 60% of maximal activity within this range, profile overview
    Bacillus subtilis 7 - 9.5 BsHSD is maximally active in L-HSE oxidation at pH 9.0 and is the least active at pH 7.0 with only 1.1% of the maximal activity
    Thermophilic bacterium 8 - 10

Associated Proteins

Protein name Organism
Homoserine dehydrogenase Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / LMG 3730 / NCIMB 10025)
Probable homoserine dehydrogenase Fission yeast
Bifunctional aspartokinase/homoserine dehydrogenase 1 Escherichia coli (strain K12)
Bifunctional aspartokinase/homoserine dehydrogenase, chloroplastic Wild carrot
Bifunctional aspartokinase/homoserine dehydrogenase 2 Escherichia coli (strain K12)