Abstract
Histidine decarboxylase (HDC; EC 4.1.1.22), an enzyme that catalyzes histamine synthesis with high substrate specificity, is a pyridoxal 5′-phosphate-dependent decarboxylase. In this article, catalytically important residues of human HDC identified in our previous works were summarized. The S354G mutation at the active site caused decreased affinity for L-histidine but acquired an ability to bind to L-dopa as a substrate and to act on the substrate. The Y334F mutation on a catalytically important loop at the active site allowed to catalyze the decarboxylation-dependent oxidative deamination of histidine to yield imidazole acetaldehyde.
In this article, human HDC inhibitors derived from the natural products were also summarized. Two ellagitannins, rugosin A, and rugosin D, which were isolated from the extract of the petal of meadowsweet, and rugosin G, an ellagitannin trimer, which was isolated from the water soluble fraction of red rose petals, were potent and promising inhibitors of human HDC.
