Structural analysis of the human histidine decarboxylase Y334F mutant

Structural analysis of the HDC Y334F mutant

抄録

Histamine is an important chemical messenger involved in a wide variety of physiological reactions. L-histidine decarboxylase (HDC) is the primary enzyme responsible for the synthesis of histamine from histidine in a one-step reaction. So far, the crystal structure of human HDC complex with the inhibitor has been determined, and the tyrosine residue (Y334) in the catalytic loop is suggested to play an important role in the decarboxylation reaction. In this study, Y334F, a point mutant of human HDC was subjected to X-ray crystallographic analysis under the same crystallization conditions that were used for the HDC–inhibitor complex; however, despite maintaining the same conditions, different types of crystals of the Y334F mutant were obtained. Furthermore, the structure of the reaction intermediate was determined by soaking the substrate histidine into the crystal of Y334F mutant. In this study, we discuss the role of the catalytic loop in histidine decarboxylation based on the structure of the reaction intermediate.