For TG derivatives to retain their potency, incorporated groups must be able to be accommodated without disrupting the canonical SERCA-TG interaction -a function of both the site of modification (O-8) and linker length. With this in mind, these two E2(AzTG) structures offer a potential explanation as to why AzTG-4 and AzTG-6 were significantly more potent than AzTG-2.