Hypoxia-inducible factor-proline dioxygenase

Hypoxia-inducible factor-proline dioxygenase
Identifiers
EC number 1.14.11.29
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

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).[1][2][3][4][5][6] This enzyme catalyses the following chemical reaction

hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2

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

In humans, there are three isoforms of hypoxia-inducible factor-proline dioxygenase. These are PHD1, PHD2 and PHD3. PHD2, in particular, was identified as the most important human oxygen sensors due to its slow reaction with oxygen.[7]


References

  1. ↑ 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.; Ratcliffe, P.J. (2001). "Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation". Science. 292 (5516): 468–472. Bibcode:2001Sci...292..468J. doi:10.1126/science.1059796. PMID 11292861.
  2. ↑ Ivan, M.; Kondo, K.; Yang, H.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J.M.; Lane, W.S.; Kaelin, W.G. (2001). "HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing". Science. 292 (5516): 464–468. Bibcode:2001Sci...292..464I. doi:10.1126/science.1059817. PMID 11292862.
  3. ↑ Bruick, R.K.; McKnight, S.L. (2001). "A conserved family of prolyl-4-hydroxylases that modify HIF". Science. 294 (5545): 1337–1340. Bibcode:2001Sci...294.1337B. doi:10.1126/science.1066373. PMID 11598268.
  4. ↑ 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.; Ratcliffe, P.J. (2001). "C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation". Cell. 107 (1): 43–54. doi:10.1016/S0092-8674(01)00507-4. PMID 11595184.
  5. ↑ Oehme, F.; Ellinghaus, P.; Kolkhof, P.; Smith, T.J.; Ramakrishnan, S.; Hutter, J.; Schramm, M.; 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 (2): 343–349. doi:10.1016/S0006-291X(02)00862-8. PMID 12163023.
  6. ↑ McNeill, L.A.; Hewitson, K.S.; Gleadle, J.M.; Horsfall, L.E.; Oldham, N.J.; Maxwell, P.H.; Pugh, C.W.; Ratcliffe, P.J.; Schofield, C.J. (2002). "The use of dioxygen by HIF prolyl hydroxylase (PHD1)". Bioorg. Med. Chem. Lett. 12 (12): 1547–1550. doi:10.1016/S0960-894X(02)00219-6. PMID 12039559.
  7. ↑ Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J (Aug 2003). "HIF prolylhydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia". EMBO J. 22 (16): 4082–4090. doi:10.1093/emboj/cdg392. PMC 175782. PMID 12912907.
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