Hypoxia-inducible factor-asparagine dioxygenase explained

Hypoxia-inducible factor-asparagine dioxygenase
Ec Number:	1.14.11.30

Hypoxia-inducible factor-asparagine dioxygenase (HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating).^{[1] [2] [3] [4] [5] [6]} This enzyme catalyses the following chemical reaction:

hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O₂

\rightleftharpoons hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO₂

Hypoxia-inducible factor-asparagine dioxygenase contains iron, and requires ascorbate.

Notes and References

1. Mahon PC, Hirota K, Semenza GL . FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity . Genes & Development . 15 . 20 . 2675–86 . October 2001 . 11641274 . 312814 . 10.1101/gad.924501 .
2. Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM, Ratcliffe PJ, Pugh CW, Schofield CJ . Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family . The Journal of Biological Chemistry . 277 . 29 . 26351–5 . July 2002 . 12042299 . 10.1074/jbc.C200273200 . Christopher J. Schofield . free .
3. Dann CE, Bruick RK, Deisenhofer J . Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway . Proceedings of the National Academy of Sciences of the United States of America . 99 . 24 . 15351–6 . November 2002 . 12432100 . 137720 . 10.1073/pnas.202614999 . 2002PNAS...9915351D . free .
4. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML . Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch . Science . 295 . 5556 . 858–61 . February 2002 . 11823643 . 10.1126/science.1068592 . 2002Sci...295..858L . 24045310 .
5. Koivunen P, Hirsilä M, Günzler V, Kivirikko KI, Myllyharju J . Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases . The Journal of Biological Chemistry . 279 . 11 . 9899–904 . March 2004 . 14701857 . 10.1074/jbc.M312254200 . free .
6. Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ . Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha . The Journal of Biological Chemistry . 278 . 3 . 1802–6 . January 2003 . 12446723 . 10.1074/jbc.C200644200 . free .