Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human hypoxia sensor |
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| Authors: | Chen Yuan-Han Comeaux Lindsay M Eyles Stephen J Knapp Michael J |
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| Institution: | Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA. |
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| Abstract: | HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)-activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human hypoxia sensing. |
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