Inducibilni faktor hipoksije-asparagin dioksigenaza
Inducibilni faktor hipoksije-asparagin dioksigenaza (EC 1.14.11.30, HIF hidroksilaza) je enzim sa sistematskim imenom inducibilni faktor hipoksije-L-asparagin, 2-oksoglutarat:kiseonik oksidoreduktaza (4-hidroksilacija).[1][2][3][4][5][6] Ovaj enzim katalizuje sledeću hemijsku reakciju
- inducibilni faktor hipoksije-L-asparagin + 2-oksoglutarat + O2 inducibilni faktor hipoksije-(3S)-3-hidroksi-L-asparagin + sukcinat + CO2
Ovaj enzim sadrži gvožđe. Za njegov rad je neophodan askorbat. On katalizuje hidroksilaciju asparagina u C-terminalnom aktivacionom domenu HIF-alfa.
Reference
- ↑ Mahon, P.C., Hirota, K. and Semenza, G.L. (2001). „FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity”. Genes Dev. 15: 2675-2686. PMID 11641274.
- ↑ Hewitson, K.S., McNeill, L.A., Riordan, M.V., Tian, Y.M., Bullock, A.N., Welford, R.W., Elkins, J.M., Oldham, N.J., Bhattacharya, S., Gleadle, J.M., Ratcliffe, P.J., Pugh, C.W. and Schofield, C.J. (2002). „Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family”. J. Biol. Chem. 277: 26351-26355. PMID 12042299.
- ↑ Dann, C.E., 3rd, Bruick, R.K. and Deisenhofer, J. (2002). „Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway”. Proc. Natl. Acad. Sci. USA 99: 15351-15356. PMID 12432100.
- ↑ Lando, D., Peet, D.J., Whelan, D.A., Gorman, J.J. and Whitelaw, M.L. (2002). „Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch”. Science 295: 858-861. PMID 11823643.
- ↑ Koivunen, P., Hirsila, M., Gunzler, V., Kivirikko, K.I. and Myllyharju, J. (2004). „Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases”. J. Biol. Chem. 279: 9899-9904. PMID 14701857.
- ↑ Elkins, J.M., Hewitson, K.S., McNeill, L.A., Seibel, J.F., Schlemminger, I., Pugh, C.W., Ratcliffe, P.J. and Schofield, C.J. (2003). „Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 α”. J. Biol. Chem. 278: 1802-1806. PMID 12446723.
Literatura
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