Sandbox Prolyl Hydroxylase Domain (PHD) Enzyme
From Proteopedia
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One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground]. | One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground]. | ||
| - | Metazoans adapt to oxygen levels in the environment by making use of intracellular oxygen levels as signals to regulate the [[transcription]] of genes essential under normoxic or [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxic] conditions. Central to this mechanism is the oxygen-dependent hydroxylation on specific proline and asparagine residues of hypoxia-inducible factor [http://en.wikipedia.org/wiki/HIF1A (HIF)- | + | Metazoans adapt to oxygen levels in the environment by making use of intracellular oxygen levels as signals to regulate the [[transcription]] of genes essential under normoxic or [http://en.wikipedia.org/wiki/Hypoxia_(medical) hypoxic] conditions. Central to this mechanism is the oxygen-dependent hydroxylation on specific proline and asparagine residues of the transcription factor, hypoxia-inducible factor [http://en.wikipedia.org/wiki/HIF1A (HIF)-α].<ref name="pmid18259202">{{cite journal | author = Fong GH, Takeda K | title = Role and Regulation of Prolyl Hydroxylase Domain Proteins | journal = Cell Death and Differentiation | volume = 15 | issue = | pages = 635–641 | year = 2008 | month = February | pmid = 18259202 | doi = 10.1038/cdd.2008.10 | url = | issn = }}</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-dependent [http://en.wikipedia.org/wiki/Oxygenase dioxygenase] that catalyzes the ''trans''-4-hydroxylation of the specific proline residues (either Pro-402 or Pro-564) in | + | '''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 the specific proline residues (in humans, either Pro-402 or 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. |
In mammals, this dioxygenase subfamily originally includes three homolog members but was recently updated: PHD1 (also known as HPH3 and [[EGLN2]]), PHD2 (also known as HPH2 and [[EGLN1]]), PHD3 (also known as HPH1 and [[EGLN3]]), and a newly identified enzyme called P4H-TM (also named as PHD4 and EGLN4).<ref name="pmid18259202">{{cite journal | author = Fong GH, Takeda K | title = Role and Regulation of Prolyl Hydroxylase Domain Proteins | journal = Cell Death and Differentiation | volume = 15 | issue = | pages = 635–641 | year = 2008 | month = February | pmid = 18259202 | doi = 10.1038/cdd.2008.10 | url = | issn = }} | In mammals, this dioxygenase subfamily originally includes three homolog members but was recently updated: PHD1 (also known as HPH3 and [[EGLN2]]), PHD2 (also known as HPH2 and [[EGLN1]]), PHD3 (also known as HPH1 and [[EGLN3]]), and a newly identified enzyme called P4H-TM (also named as PHD4 and EGLN4).<ref name="pmid18259202">{{cite journal | author = Fong GH, Takeda K | title = Role and Regulation of Prolyl Hydroxylase Domain Proteins | journal = Cell Death and Differentiation | volume = 15 | issue = | pages = 635–641 | year = 2008 | month = February | pmid = 18259202 | doi = 10.1038/cdd.2008.10 | url = | issn = }} | ||
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=== '''Structure''' === | === '''Structure''' === | ||
| + | The protein core () of PHDs consists of eight β-strands in a "jelly-roll" or double stranded β helix (DBSH) fold motif which is typical of 2-OG-dependent oxygenases. Contained in this core () are the three Fe(II)-binding ligands formed by the conserved triad motif, His-X-Asp/Glu-Xn-His. Three conserved α-helices support the DBSH core. | ||
Revision as of 20:07, 30 April 2010
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| 2g19, resolution 1.70Å () | |||||||||
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| Ligands: | , | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.
Metazoans adapt to oxygen levels in the environment by making use of intracellular oxygen levels as signals to regulate the transcription of genes essential under normoxic or hypoxic conditions. Central to this mechanism is the oxygen-dependent hydroxylation on specific proline and asparagine residues of the transcription factor, hypoxia-inducible factor (HIF)-α.[1]
Prolyl hydroxylase domain (PHD) enzyme (EC 1.14.11.-) is a Fe(II)/2-oxoglutarate (OG)-dependent dioxygenase that catalyzes the trans-4-hydroxylation of the specific proline residues (in humans, either Pro-402 or Pro-564) in (HIF)-α. In addition to iron, this enzyme also requires ascorbate as a cofactor.
In mammals, this dioxygenase subfamily originally includes three homolog members but was recently updated: PHD1 (also known as HPH3 and EGLN2), PHD2 (also known as HPH2 and EGLN1), PHD3 (also known as HPH1 and EGLN3), and a newly identified enzyme called P4H-TM (also named as PHD4 and EGLN4).[1]
