Human Galactose-1-phosphate uridylyltransferase (GALT), Galactokinase 1 (GALK1)
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TEP details
Summary
This project describes a drug discovery plan for Classic Galactosemia, a rare disorder of galactose metabolism where there is currently no disease-transforming therapy. This TEP provides the protein reagents, biophysical assays, and structural information to facilitate two aspects of galactosemia research: (i) to understand the molecular basis of the disease due to defective GALT enzyme, and (ii) to provide chemical starting points to explore metabolic intervention of the upstream enzyme GALK1 aimed at mitigating the GALT defect (substrate reduction).
Structures
Structural data available in TEP:
GALT, enzyme defective in galactosemia:
- Uridylylated hGALT bound with glucose-1-phosphate (PDB:5IN3 ): protein, ligand
- hGALT with epitope mutations A21Y:A22T:T23P:R25L (PDB:6GQD ): protein, ligand
GALK1, potential therapeutic target:
- hGALK1 bound with galactose and ADP (PDB:6GR2 ): protein, ligand
- hGALK1 bound with galactose and Fragment a (N-(Cyclobutylmethyl)-1,5-dimethyl-1H-pyrazole-4-carboxamide, x717) (PDB:6Q8Z ): protein, ligand
- hGALK1 bound with galactose and Fragment b (4-{[2-(Methylsulfonyl)-1H-imidazol-1-yl]methyl}-1,3-thiazole, x843) (PDB:6QJE ): protein, ligand
- hGALK1 bound with galactose and Fragment c (Ethyl 1-(2-pyrazinyl)-4-piperidinecarboxylate, x682) (PDB:6Q3W ): protein, ligand
- hGALK1 bound with galactose and Fragment d (1-(4-Methoxyphenyl)-3-(4-pyridinyl)urea, x747) (PDB:6Q90 ): protein, ligand
- hGALK1 bound with galactose and Fragment e (5-Chloro-N-isobutyl-2-methoxybenzamide, x841) (PDB:6Q91 ): protein, ligand