pH-induced structural changes regulate histidine decarboxylase activity inLactobacillus 30a

Histidine decarboxylase (HDC) from Lactobacillus 30a produces histamine tha t is essential to counter waste acids, and to optimize cell growth. The HDC trimer is active at low PH and inactive at neutral to alkaline pH. We have solved the X-ray structure of HDC at pH 8 and revealed the novel mechanism of PH regulation. At high PH helix B is unwound, destroying the substrate binding pocket. At acid pH the helix is stabilized, partly through protonat ion of Asp198 and Asp53 on either side of the molecular interface, acting a s a proton trap. In contrast to hemoglobin regulation, pH has a large effec t on the tertiary structure of HDC monomers and relatively little or no eff ect on quaternary structure. (C) 2001 Academic Press.