Biogenesis of TPQ and Related Cofactors

His 689 and the O4 of TPQ support a model in which the first step in TPQ biogenesis is binding of Cu to tyrosine (Tyr 466 in ECAO) and the three His ligands. A chemical mechanism for the subsequent oxidation steps involving free radical intermediates has been proposed (Dooley, 1999). 

FIGURE 15. Possible mechanism for biogenesis of TPQ (from Dooley, 1999 with permission). 

The biogenesis of the LTQ cofactor in lysyl oxidase may be closely similar to that of TPQ since it is also derived autocatalytically from a tyrosine precursor (Wang et al, 1996). A chemically plausible mechanism has been proposed (Dooley, 1999). 

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