User:Amir Mitchell/Gal4

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Galactose Metabolism Pathway

Gal4 is a yeast transcription factor. This positive regulator induces the Leloir pathway, a metabolic pathway for the conversion of β-d-galactose to the glucose-1-phosphate. The pathway is comprised of four enzymes: (1) Galactokinase (Gal1), (2) Galactose-1-phosphate uridylyltransferase (Gal7) and (3) Galactose mutarotase and UDP-galactose-4-epimerase both contaied by a single polypeptide chain (Gal10). Two additional regulatory proteins, Gal80 and Gal3, interact with Gal4 to affect the expression of the pathway. Together this set of structural and regulatory genes has served as a model system for the study of transcription regulation in eukaryotes[1][2].

Regulation of the Pathway

Three factors participate comprise the regulatory circuit of the galactose pathway: the transcription activator Gal4 present in the nucleus, a signal transducer protein Gal3 present in the cytoplasm and the inhibitory protein Gal80 which undergoes rapid nuclear-cytoplasmic shuttling. In the absence of galactose, binding of Gal80 to Gal4 limits active transcription of the Gal genes. Encounter with galactose triggers a Gal3p–Gal80p interaction in the cytoplasm resulting in redistribution of Gal80 from the nucleus to the cytoplasm, thus freeing Gal4 to recruit chromatin remodeling factors and PolII and activate GAL gene transcription [3].

The Gal4 Transcription factor

The key transctiptional activator Gal4 is comprised from two separate domains: a DNA binding domain located at the N-terminus of the protein and a transcription activation domain located at the C-terminus. Additionally a dimerization domain is found between the DNA binding and transcription activation domains. Gal4 recognizes a 17 base-pair long sequence in the upstream activating sequence (uas-g) of these genes, (5'-cggrnnrcynyncnccg-3'). Gal4 binds to the DNA as a homodimer. This protein contains a fungal Zn(2)-Cys(6) binuclear cluster domain. Many transcriptional activator proteins possess such a domain in which six conserved cysteine residues bind to two zinc ions known as a binuclear zinc cluster. This cysteine-rich region binds to the DNA in a zinc-dependent fashion. While GAL4 from the organism Saccharomyces cerevisiae contains such a domain, it binds two Cadmium (Cd) ions rather than Zinc ions.


3bts, resolution 2.70Å ()
Ligands:
Gene: GAL80 (Saccharomyces cerevisiae)
Related: 3btu, 3btv
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


zinc finger

Mutation in Gal4

gal81c - constitutive [4]

References

  1. Structure and Function of Enzymes of the Leloir Pathway for Galactose Metabolism, J. Biol. Chem 2003 [1]
  2. Galactose metabolic pathway, KEGG database [2]
  3. Gene activation by interaction of an inhibitor with a cytoplasmic signaling protein [3]

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Amir Mitchell

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