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Figure 1.
The reaction catalyzed by wild-type FIH (and FIH-D201G).
hydroxylation of the β-carbon of Asn-803 within the C-terminal
transactivation domain of HIF-1α. The reaction requires Fe(II)
as a cofactor and dioxygen and 2OG as co-substrates that are
converted to succinate and carbon dioxide concomitant with
hydroxylation of HIF-1α substrate. For the FIH-D201A/E
variants, 2OG decarboxylation is uncoupled from the
hydroxylation of HIF-1α substrate and is stimulated by the
presence of a reducing agent (ascorbate or DTT).
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