User:Cornelius Taabazuing/sandbox 1
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| Human HIF complex with Fe+2, sulfate and alpha ketogluterate, 1h2l | |||||||||
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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 HIFFactor Inhibiting HIF
Hypoxia Inducible Factor (HIF)is a heterodimeric transcription factor that regulates over 100 genes. HIF consists of a constitutively expressed beta subunit, and an alpha subunit that is regulated in oxygen dependent manor. There are two enzymes that regulate HIF controlled gene expression, Factor Inhibiting HIF (FIH) and Prolyl Hydroxylase Domain 2 (PHD2). During normoxic conditions, Hydroxylation of one of two or both proline residues in the Oxygen Degradation Domain (ODD) of HIF results in proteosomal degradation of the HIF alpha subunit. Hydroxylation of an asparagine residue in the C-terminal Trans-Activation Domain () of HIF by FIH results in transcriptional silencing of genes due to HIF's inability to recruit the co-activator p300. However, under hypoxic conditions, there is no hydroxylation, resulting in stabilization of the HIF alpha subunit. The alpha subunit dimerizes with the beta subunit and HIF is able to transcribe genes important for red blood cell production, metabolic activity, angiogenesis,development, and many other functions.
Active SiteActive 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 SurfaceEnzyme Surface
In this depiction, the (JH) of FIH is shown.
3D structures of HIF3D structures of HIF
Additional ResourcesAdditional Resources
For additional information, see: Cancer