Abstract
The Gal1p (Galactokinase) protein is known for regulation of D-galactose metabolism. It catalyzes the formation of galactose -1-phosphate from alpha - D-galactose, which is an important step in galactose catabolism. The knowledge of Gal1p protein structure, its protein interacting partners and enumeration of functional site residues will provide great insight in understanding the functional role of Gal1p. These studies are lacking in case of the Gal11p kinase enzyme. Structure of this enzyme has already been determined in S. cerevisiae, however, no structural information for this protein is available for K. lactis and E. coli. We used the homology modeling based approach to model the structures of Gal1p for K. lactis and E. coli. Furthermore, functional residues were predicted for these Gal1 proteins and the strength of interaction between Gal1p and other Gal proteins was determined by protein-protein interaction studies via patchdock software. The interaction studies revealed that the affinity for Gal1p for other Gal proteins varies in different organisms. Sequence and structural based comparison of Gal1p kinase enzyme showed that the orthologs in K.lactis and S. cervisiae are more similar to each other as compared to the ortholog in E. coli. These studies carried out by us will help in better understanding of the galactose metabolism. Our sequence and structure comparison studies revealed that Human Gal1p shows more homology for Gal1p protein of E. coli. The above studies may be applied to Human Gal1p, where it can help in gaining useful insight into Galactosemia disease.
Highlights
In Saccharomyces cerevisiae, the GAL1 gene is one of the structural gene of the galactose pathway along with GAL7, GAL10 and GAL2 [1, 2]
The 3D model structures of Gal1p from Kluyveromyces lactis and E. coli were generated by swiss model software and EsyPred3D (Modeller 6v2) via homology modeling (Figure 2)
Gal1p is a Galactokinase enzyme which participates in Leloir pathway of D- Galactose metabolism
Summary
In Saccharomyces cerevisiae, the GAL1 gene is one of the structural gene of the galactose pathway along with GAL7, GAL10 and GAL2 [1, 2]. These structural genes are regulated at the transcriptional level in response to Gal4p, Gal80p and Gal3p [3]. The Gal4p acts as a transcriptional activator[4]. Gal80p acts as transcriptional repressor[5]. Gal3p acts as a ligand sensor where it sequesters Gal80p in the cytoplasm[6]. As a result of this effect Gal4p becomes active and turns on the synthesis of GAL genes that metabolized the galactose [7]
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