Hypoxia-inducible factor-asparagine dioxygenase

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Hypoxia-inducible factor-asparagine dioxygenase
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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). [1] [2] [3] [4] [5] [6] This enzyme catalyses the following chemical reaction:

hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2

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

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<span class="mw-page-title-main">HIF prolyl-hydroxylase inhibitor</span>

Not to be confused with Factor Inhibiting HIF Asparaginyl Hydroxylase Inhibitors

mir-210 microRNA

In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Hypoxia-inducible factor-proline dioxygenase (EC 1.14.11.29, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction

Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. Both use O2 and reducing equivalents as cosubstrates and both generate water.

Christopher Joseph Schofield is a Professor of Chemistry at the University of Oxford and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry and a Fellow of Hertford College. Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new possibilities in antibiotic research, oxygen sensing, and gene regulation.

<span class="mw-page-title-main">P4HTM</span> Protein-coding gene in the species Homo sapiens

Prolyl 4-hydroxylase, transmembrane is a protein that in humans is encoded by the P4HTM gene.

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.