Molecular Playground/FIH
From Proteopedia
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| - | {{STRUCTURE_1h2l| PDB=1h2l | SIZE=300| SCENE=User:John_Hangasky/Sandbox_1/Fih/4|right| CAPTION=Human | + | {{STRUCTURE_1h2l| PDB=1h2l | SIZE=300| SCENE=User:John_Hangasky/Sandbox_1/Fih/4|right| CAPTION=Human FIH complex with HIF, Fe+2, sulfate and 2-oxoglutaric acid, [[1h2l]] }} |
=== Factor Inhibiting HIF === | === Factor Inhibiting HIF === | ||
Revision as of 10:21, 25 January 2012
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| Human FIH complex with HIF, Fe+2, sulfate and 2-oxoglutaric acid, 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 | ||||||||
Contents |
Factor 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 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 active site ligands can be seen . The axial coordination position is initially occupied by a water molecule. Upon binding of CTAD, this water molecule is released, opening a coordination site for oxygen to bind.
Enzyme Surface
In this depiction, the of FIH is shown.
3D structures of HIF
Additional Resources
For additional information, see: Cancer
Proteopedia Page Contributors and Editors (what is this?)
Vanessa Chaplin, John Hangasky, Michal Harel, Cornelius Taabazuing, David Canner, Breanne Holmes UMass-Amherst
