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.