Human alpha-aminoadipic semialdehyde synthase (AASS); A Target Enabling Package

<p>This work provides the early tools to develop substrate reduction inhibitors for a genetic childhood seizure disorder, with the hypothesis to target the enzyme (AASS) upstream of the defective gene (ALDH7A1) in the human lysine metabolic pathway. This TEP package includes recombinant human AASS purification protocols, structures of the AASS second domain in different states, in vitro assays to detect ligand binding (differential scanning fluorimetry) and enzyme activity (NADH formation) of human AASS, as well as initial chemical matters.</p

Human alpha-aminoadipic semialdehyde synthase (AASS); A Target Enabling Package

<p>This work provides the early tools to develop substrate reduction inhibitors for a genetic childhood seizure disorder, with the hypothesis to target the enzyme (AASS) upstream of the defective gene (ALDH7A1) in the human lysine metabolic pathway. This TEP package includes recombinant human AASS purification protocols, structures of the AASS second domain in different states, in vitro assays to detect ligand binding (differential scanning fluorimetry) and enzyme activity (NADH formation) of human AASS, as well as initial chemical matters.</p

Plant Growth Regulator Daminozide Is a Selective Inhibitor of Human KDM2/7 Histone Demethylases

The JmjC oxygenases catalyze the <i>N</i>-demethylation of <i>N</i>^ε-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (<i>N-</i>(dimethylamino)­succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups