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.

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 [1][2].

These events lead to a reduced probability of binding between Gal80p and Gal4p. Subsequently, recruitment of chromatin remodeling factors and PolII holoenzyme activate GAL gene transcription.

The Gal4 Transcription factor

In the presence of galactose Gal4 recognizes and binds to specific upstream activation sequences of the GAL structural genes (UAS-GAL) through a DNA-binding domain. In the absence of galactose, Gal4 interacts with Gal80 also present in the nucleus.


PDB ID 1d66

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1d66, resolution 2.70Å ()
Ligands:
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


zinc finger

Mutation in Gal4

gal81c - constitutive [3]

References

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

Galactose metabolic pathway, KEGG database [4].

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Amir Mitchell

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