An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae. diphthamide-[translation elongation factor 2] + NAD(+) = H(+) + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2] + nicotinamide Partially inhibited by 1,8-naphthalimide (NAP). For ADP-ribosyltransferase activity of a catalytic fragment of residues 459-666. Probably requires further proteolytic processing to generate a fragment with toxic activity. Exotoxins are often highly strain specific; not encoded in strain ATCC 39315 / El Tor Inabe N16961.