Structural Research of Glucosyltransferases

Glucosyltransferases play a vital role in the process of N-glycosylation, a post-translational modification essential for the proper folding, stability, and function of glycoproteins in eukaryotic cells. Understanding the structural characteristics and mechanisms of these enzymes is crucial for unraveling the intricacies of N-glycosylation and its implications in various biological processes and diseases. N-Glycosylation involves the addition of glycan chains to specific asparagine residues on nascent glycoproteins. Glucosyltransferases are responsible for catalyzing the transfer of glucose moieties onto the glycan structure. This process occurs primarily in the lumen of the endoplasmic reticulum (ER) and is crucial for the quality control and maturation of glycoproteins.

Understanding the Architecture of Glucosyltransferases

Researchers have made significant progress in elucidating the structural characteristics of glucosyltransferases. Cryo-electron microscopy (cryo-EM) has emerged as a powerful technique for visualizing these enzymes at high resolution. A notable study presented the cryo-EM structure of yeast ALG6, a glucosyltransferase involved in N-glycosylation, at a resolution of 3.0 Å. This breakthrough revealed a previously undescribed transmembrane protein fold, providing valuable insights into the architecture of this crucial enzyme.

Modular Architecture of Glucosyltransferases

Further investigations into the structure of glucosyltransferases have unveiled their modular architecture. Studies suggest that these enzymes, including those belonging to the C-superfamily (GT-Cs), consist of a conserved module and a variable module. The conserved module plays a fundamental role in the catalytic mechanism, while the variable module contributes to substrate recognition and specificity. This modular architecture allows for the diverse functions and activities exhibited by different glucosyltransferases.

Active Site Insights

By employing cryo-EM in combination with synthetic analogues and enzymatic glycan extension, researchers have gained valuable insights into the active sites of glucosyltransferases. Another cryo-EM study, successfully visualized ALG6 bound to an analogue of dolichylphosphate-glucose at a resolution of 3.9 Å. This detailed structure provided a clearer understanding of the catalytic mechanism and identified a conserved catalytic aspartate residue that likely acts as a general base in the enzymatic reaction.

Figure 1. ALG6 structure and GT-C architecture. (Bloch J S, et al., 2020)

Table 1. Structural Research of Glucosyltransferases.

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Reference

1. Bloch J S, et al. Structure and mechanism of the ER-based glucosyltransferase ALG6. Nature. 2020, 579(7799): 443-447.