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Publication Abstract from PubMed

Histamine is an important chemical mediator for a wide variety of physiological reactions. L-histidine decarboxylase (HDC) is the primary enzyme responsible for histamine synthesis and produces histamine from histidine in a one-step reaction. In this study, we determined the crystal structure of human HDC (hHDC) complexed with the inhibitor histidine methyl ester (HME). This structure shows the detailed features of the pyridoxal-5'-phosphate (PLP)-inhibitor adduct (external aldimine) at the active site of HDC. Moreover, a comparison of the structures of hHDC and aromatic L-amino acid (L-dopa) decarboxylase showed that Ser354 (S345) was a key residue for substrate specificity. The S354G mutation at the active site enlarged the size of the hHDC substrate-binding pocket and resulted in a decreased affinity for histidine, but an acquired ability to bind and act on L-dopa as a substrate. These data provide insight into the molecular basis of substrate recognition among the group II PLP-dependent decarboxylases.

Structural study reveals Ser345 determines substrate specificity on human histidine decarboxylase.,Komori H, Nitta Y, Ueno H, Higuchi Y J Biol Chem. 2012 Jul 5. PMID:22767596^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.