passages.id: split_4_validation_1211_passage
passages.type: progene_text
passages.text: Major differences between proposed DHF mechanisms are whether the carboxylate group of the conserved active - site Asp or Glu residue is protonated or ionized during the reaction , and whether there is direct protonation of N5 or a proton shuttle from an initially protonated carboxylate group via O4 .