Inducibilni faktor hipoksije-prolin dioksigenaza
Inducibilni faktor hipoksije-prolin dioksigenaza (EC 1.14.11.29, HIF hidroksilaza) je enzim sa sistematskim imenom inducibilni faktor hipoksije-L-prolin, 2-oksoglutarat:kiseonik oksidoreduktaza (4-hidroksilacija).[1][2][3][4][5][6] Ovaj enzim katalizuje sledeću hemijsku reakciju
- inducibilni faktor hipoksije-L-prolin + 2-oksoglutarat + O2 inducibilni faktor hipoksije-trans-4-hidroksi-L-prolin + sukcinat + CO2
Ovaj enzim sadrži gvožđe. Za njegov rad je neophodan askorbat. On specifično vrši hidroksilaciju prolinskog ostataka u HIF-alfa, alfa podjedinici transkripcionog regulatora HIF (inducibilnog faktora hipoksije).
Reference
- ^ Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim Av, Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W. and Ratcliffe, P.J. (2001). „Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation”. Science. 292: 468—472. PMID 11292861.
- ^ Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S. and Kaelin , W.G., Jr. (2001). „HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing”. Science. 292: 464—468. PMID 11292862.
- ^ Bruick, R.K. & McKnight, S.L. (2001). „A conserved family of prolyl-4-hydroxylases that modify HIF”. Science. 294: 1337—1340. PMID 11598268.
- ^ Epstein, A.C., Gleadle, J.M., McNeill, L.A., Hewitson, K.S., O'Rourke, J., Mole, D.R., Mukherji, M., Metzen, E., Wilson, M.I., Dhanda, A., Tian, Y.M., Masson, N., Hamilton, D.L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P.H., Pugh, C.W., Schofield, C.J. and Ratcliffe, P.J. (2001). „C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation”. Cell. 107: 43—54. PMID 11595184.
- ^ Oehme, F., Ellinghaus, P., Kolkhof, P., Smith, T.J., Ramakrishnan, S., Hutter, J., Schramm, M. and Flamme, I. (2002). „Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors”. Biochem. Biophys. Res. Commun. 296: 343—349. PMID 12163023.
- ^ McNeill, L.A., Hewitson, K.S., Gleadle, J.M., Horsfall, L.E., Oldham, N.J., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J. and Schofield, C.J. (2002). „The use of dioxygen by HIF prolyl hydroxylase (PHD1)”. Bioorg. Med. Chem. Lett. 12: 1547—1550. PMID 12039559.
Literatura
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