Vanessa Chaplin/sandbox2: Difference between revisions
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=== Introduction === | === Introduction === | ||
Metazoans adapt to oxygen levels in the environment by making use of intracellular oxygen levels as signals to regulate the [http://en.wikipedia.org/wiki/Transcription_(genetics) transcription] of genes that are essential under normoxic or [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxic] conditions. Central to this mechanism is the oxygen-dependent hydroxylation of specific proline and asparagine residues of the transcription factor, hypoxia-inducible factor [http://en.wikipedia.org/wiki/HIF1A (HIF)-α].<ref name="review">Fong, G.H., Takeda, K. "Role and Regulation of Prolyl Hydroxylase Domain Proteins." Cell Death and Differentiation, February 15, 2008, 15, 635-641. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18259202 18259202]</ref> | Metazoans adapt to oxygen levels in the environment by making use of intracellular oxygen levels as signals to regulate the [http://en.wikipedia.org/wiki/Transcription_(genetics) transcription] of genes that are essential under normoxic or [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxic] conditions. Central to this mechanism is the oxygen-dependent hydroxylation of specific proline and asparagine residues of the transcription factor, hypoxia-inducible factor [http://en.wikipedia.org/wiki/HIF1A (HIF)-α] by the HIF-hydroxylase enzymes, which are studied extensively by the [http://people.chem.umass.edu/knapplab/?q=knappchem/index.html Knapp Lab] here at UMass Amherst.<ref name="review">Fong, G.H., Takeda, K. "Role and Regulation of Prolyl Hydroxylase Domain Proteins." Cell Death and Differentiation, February 15, 2008, 15, 635-641. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18259202 18259202]</ref> | ||
'''Prolyl hydroxylase domain (PHD) enzyme''' [http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/14/11/ (EC 1.14.11.-)] is a Fe(II)/2-oxoglutarate (OG)-dependent [http://en.wikipedia.org/wiki/Oxygenase dioxygenase] that catalyzes the ''trans''-4-hydroxylation of specific proline residues (in humans, Pro-402 and Pro-564) in [http://en.wikipedia.org/wiki/HIF1A (HIF)-α]. In addition to iron, this enzyme also requires [http://en.wikipedia.org/wiki/Vitamin_C ascorbate] as a cofactor.<ref name="structure">Mcdonough, M.A., Li, V., Flashman, E., et al. "Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)." PNAS, June 27, 2006, 103 (26), 9814-9819. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16782814 16782814]</ref> | '''Prolyl hydroxylase domain (PHD) enzyme''' [http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/14/11/ (EC 1.14.11.-)] is a Fe(II)/2-oxoglutarate (OG)-dependent [http://en.wikipedia.org/wiki/Oxygenase dioxygenase] that catalyzes the ''trans''-4-hydroxylation of specific proline residues (in humans, Pro-402 and Pro-564) in [http://en.wikipedia.org/wiki/HIF1A (HIF)-α]. In addition to iron, this enzyme also requires [http://en.wikipedia.org/wiki/Vitamin_C ascorbate] as a cofactor.<ref name="structure">Mcdonough, M.A., Li, V., Flashman, E., et al. "Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)." PNAS, June 27, 2006, 103 (26), 9814-9819. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16782814 16782814]</ref> | ||
