Molecular Playground/FIH
From Proteopedia
(New page: {{STRUCTURE_1h2l| PDB=1h2l | SCENE=User:John_Hangasky/Sandbox_1/Fih/4}} === Factor Inhibiting HIF === '''H'''ypoxia '''I'''nducible '''F'''actor (HIF)is a transcription activator that re...) |
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'''H'''ypoxia '''I'''nducible '''F'''actor (HIF)is a transcription activator that regulates over 100 genes, many of which are important for development. HIF has been found to be over expressed in many cancers. '''F'''actor '''I'''nhibing '''H'''IF (FIH) is a non-heme Iron (II) α-ketoglutarate (α-KG) dependent asparaginyl hydroxylase that regulates HIF. In normoxic conditions (high oxygen concentrations), molecular oxygen is used to hydroxylate HIF, preventing HIF from binding to p300, a transcription co-activator. However, in hypoxic conditions (low oxygen concentrations), this hydroxylation does not occur. | '''H'''ypoxia '''I'''nducible '''F'''actor (HIF)is a transcription activator that regulates over 100 genes, many of which are important for development. HIF has been found to be over expressed in many cancers. '''F'''actor '''I'''nhibing '''H'''IF (FIH) is a non-heme Iron (II) α-ketoglutarate (α-KG) dependent asparaginyl hydroxylase that regulates HIF. In normoxic conditions (high oxygen concentrations), molecular oxygen is used to hydroxylate HIF, preventing HIF from binding to p300, a transcription co-activator. However, in hypoxic conditions (low oxygen concentrations), this hydroxylation does not occur. | ||
| - | FIH binds to the C-terminal Activation Domain (CTAD) of HIF. This binding domain, <scene name='User:John_Hangasky/Sandbox_1/Fih/5'>CTAD</scene>, is colored teal in this depiction. | + | FIH binds to the C-terminal Activation Domain (CTAD) of HIF. This binding domain, <scene name='User:John_Hangasky/Sandbox_1/Fih/5'>CTAD</scene>, (JH)is colored teal in this depiction. |
=== Active Site=== | === Active Site=== | ||
| - | The <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site/4'>FIH Active Site</scene> contains an Iron (II) core. The Iron core is coordinated by 2 histidine residues, an aspartate residue, an α-ketoglutarate molecule, and one water molecule. The Iron (II) is six coordinated, with α-KG chelating in a bidentate manner. In the depiction of the <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site_ligands/5'>FIH Active Site Ligands</scene> Histidines are colored blue, Aspartate is colored red, Iron is the white sphere, and α-KG is colored yellow. The sixth coordination site is usually occupied by water, not shown here. | + | The <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site/4'>FIH Active Site</scene> (CT)contains an Iron (II) core. The Iron core is coordinated by 2 histidine residues, an aspartate residue, an α-ketoglutarate molecule, and one water molecule. The Iron (II) is six coordinated, with α-KG chelating in a bidentate manner. In the depiction of the <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site_ligands/5'>FIH Active Site Ligands</scene> (BH) Histidines are colored blue, Aspartate is colored red, Iron is the white sphere, and α-KG is colored yellow. The sixth coordination site is usually occupied by water, not shown here. |
=== Enzyme Surface === | === Enzyme Surface === | ||
| - | In this depiction, the <scene name='User:John_Hangasky/Sandbox_1/Fih_surface/4'>solvent accessible surface</scene> of FIH is shown. | + | In this depiction, the <scene name='User:John_Hangasky/Sandbox_1/Fih_surface/4'>solvent accessible surface</scene> (JH) of FIH is shown. |
Revision as of 16:34, 13 May 2010
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| 1h2l, resolution 2.25Å () | |||||||||
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| Ligands: | , , | ||||||||
| Related: | 1d7g, 1h2k, 1h2m, 1h2n, 1l8c, 1lm8, 1lqb | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Factor Inhibiting HIF
Hypoxia Inducible Factor (HIF)is a transcription activator that regulates over 100 genes, many of which are important for development. HIF has been found to be over expressed in many cancers. Factor Inhibing HIF (FIH) is a non-heme Iron (II) α-ketoglutarate (α-KG) dependent asparaginyl hydroxylase that regulates HIF. In normoxic conditions (high oxygen concentrations), molecular oxygen is used to hydroxylate HIF, preventing HIF from binding to p300, a transcription co-activator. However, in hypoxic conditions (low oxygen concentrations), this hydroxylation does not occur.
FIH binds to the C-terminal Activation Domain (CTAD) of HIF. This binding domain, , (JH)is colored teal in this depiction.
Active Site
The (CT)contains an Iron (II) core. The Iron core is coordinated by 2 histidine residues, an aspartate residue, an α-ketoglutarate molecule, and one water molecule. The Iron (II) is six coordinated, with α-KG chelating in a bidentate manner. In the depiction of the (BH) Histidines are colored blue, Aspartate is colored red, Iron is the white sphere, and α-KG is colored yellow. The sixth coordination site is usually occupied by water, not shown here.
Enzyme Surface
In this depiction, the (JH) of FIH is shown.
Proteopedia Page Contributors and Editors (what is this?)
Vanessa Chaplin, John Hangasky, Michal Harel, Cornelius Taabazuing, David Canner, Breanne Holmes UMass-Amherst
