Diphthamide biosynthesis protein 7 (DPH7)

Diphthamide biosynthesis protein 7 is an enzyme essential for the biosynthesis of diphthamide, a unique post-translationally modified histidine residue present on translation elongation factor 2 (eEF2)[1][2][3]. Diphthamide on eEF2 is the target of diphtheria toxin. DPH7 contains a WD40 repeat domain and acts as a methylesterase. It catalyzes the hydrolysis of methylated diphthine (an intermediate generated by Dph5), converting it into diphthine, which is then available for subsequent amidation by Dph6, ultimately yielding diphthamide[1][2][3]. DPH7's enzymatic function is required for complete diphthamide maturation, critical for normal translational fidelity and resistance to diphtheria toxin. Unlike classic methyltransferases, DPH7's methylesterase activity is biochemically unique within the WD40 protein family[1][2]. Mutations or dysregulation of DPH7 have been associated with certain developmental syndromes and cancer, but it is not known to be a direct therapeutic target or drug-binding protein[3].

Other names

Diphthine methyltransferaseWD repeat-containing protein 85WDR85C9orf112FLJ90634RRT2