126.96.36.199 - Homoserine dehydrogenase
There are no alternative names for this Enzyme
L-homoserine + NAD(+) = H(+) + L-aspartate 4-semialdehyde + NADH
There are no Cofactors for this Enzyme
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.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
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
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
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
- Heterologous overexpression and characterization of homoserine dehydrogenase from Paracoccidioides brasiliensis.
- Virtual screening and repurposing of approved drugs targeting homoserine dehydrogenase from Paracoccidioides brasiliensis.
- Conformational changes in the catalytic region are responsible for heat-induced activation of hyperthermophilic homoserine dehydrogenase.
- Molecular and Enzymatic Features of Homoserine Dehydrogenase from Bacillus subtilis.
- Expression, purification, and biochemical characterization of an NAD+-dependent homoserine dehydrogenase from the symbiotic Polynucleobacter necessarius subsp. necessarius.
- Characterization of a Novel Type Homoserine Dehydrogenase Only with High Oxidation Activity from Arthrobacter nicotinovorans
- Biochemical characterization and redesign of the coenzyme specificity of a novel monofunctional NAD+-dependent homoserine dehydrogenase from the human pathogen Neisseria gonorrhoeae.
- New inhibitors of homoserine dehydrogenase from Paracoccidioides brasiliensis presenting antifungal activity.
- The crystal structure of homoserine dehydrogenase complexed with l-homoserine and NADPH in a closed form.
- Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase.
- Inhibition of homoserine dehydrogenase by formation of a cysteine-NAD covalent complex.