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Hypoxia-inducible factor-asparagine dioxygenase

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Hypoxia-inducible factor-asparagine dioxygenase
Identifiers
EC no.1.14.11.30
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Hypoxia-inducible factor-asparagine dioxygenase (EC 1.14.11.30, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction:

hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 {\displaystyle \rightleftharpoons } hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2

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

References

  1. Mahon PC, Hirota K, Semenza GL (October 2001). "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. doi:10.1101/gad.924501. PMC 312814. PMID 11641274.
  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 (July 2002). "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. doi:10.1074/jbc.C200273200. PMID 12042299.
  3. Dann CE, Bruick RK, Deisenhofer J (November 2002). "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. Bibcode:2002PNAS...9915351D. doi:10.1073/pnas.202614999. PMC 137720. PMID 12432100.
  4. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (February 2002). "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch". Science. 295 (5556): 858–61. Bibcode:2002Sci...295..858L. doi:10.1126/science.1068592. PMID 11823643. S2CID 24045310.
  5. Koivunen P, Hirsilä M, Günzler V, Kivirikko KI, Myllyharju J (March 2004). "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. doi:10.1074/jbc.M312254200. PMID 14701857.
  6. Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ (January 2003). "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. doi:10.1074/jbc.C200644200. PMID 12446723.

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Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11: 2-oxoglutarate
1.14.13: NADH or NADPH
1.14.14: reduced flavin or flavoprotein
1.14.15: reduced iron–sulfur protein
1.14.16: reduced pteridine (BH4 dependent)
1.14.17: reduced ascorbate
1.14.18-19: other
1.14.99 - miscellaneous
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