User:John Hangasky/Sandbox 1
From Proteopedia
| (8 intermediate revisions not shown.) | |||
| Line 3: | Line 3: | ||
=== Factor Inhibiting HIF === | === Factor Inhibiting HIF === | ||
| - | '''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 dependent asparaginyl hydroxylase that regulates HIF. In normoxic conditions (high oxygen | + | '''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 | + | 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. |
=== Active Site=== | === Active Site=== | ||
| - | The <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site/ | + | The <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site/6'>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. The coordination of the <scene name='User:John_Hangasky/Sandbox_1/Fih_active_site_ligands/6'>active site ligands</scene> are seen here. The sixth coordination site is usually occupied by water, not shown here. Upon binding of substrate, it is believed this water is released and the iron becomes five coordinate. |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
| |||||||||
| 1h2l, resolution 2.25Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||||
| Related: | 1d7g, 1h2k, 1h2m, 1h2n, 1l8c, 1lm8, 1lqb | ||||||||
| |||||||||
| |||||||||
| 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, , is colored teal in this depiction.
Active Site
The 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. The coordination of the are seen here. The sixth coordination site is usually occupied by water, not shown here. Upon binding of substrate, it is believed this water is released and the iron becomes five coordinate.
