Conclusion:

Aspartylglucosaminidase is an important lysosomal hydrolase that is involved in glycoprotein degradation. A deficiency of this enzyme causes AGU (aspartylglucosaminuria). It has been shown through many experiments that mutations induced into the polypeptide by substitution of amino acids cause either a decrease in AGA acitivity or a complete loss of activity. It is believed that these mutations result in misfolding or changes in flexibiltiy of the polypeptide due to substitutions of important amino acids in the active site. His204 is located right next to the active site and is of essential importance for the normal intracellular processing of AGA. It is "thought to be a prerequisite for the function of a specific protease responsible for the cleavage of the precursor polypeptide." It was found that subtitution of the His204 resulted in the blockage of cleavage of AGA into subunits.(4) It was also found that substitution of Trp11 (which participates in the carbohydrate binding) with phenylalanine or serine results in an inactive enzyme. Removal of the disulphide bond between Cys140 and Cys156 (by a mutation introduced to Cys140) leads to the decreased solubitlity of the enzyme by affecting the conformation of the peptide. This decreased solubility also decreases the proteolytic activation of the AGA precursor and causes the mutant polypeptide to build up and thus be retained in the endoplasmic reticulum.(6) "The disulphide bridge between Cys286 and Cys306 seem only to be involved with stabilization of the tertiary structure of the enzyme but substitution of Cys306 by an arginine residue, found in an American AGU patient disturbs the folding of the precursor and prevents its proteolytic activation in the ER."(3) "None of the known AGU mutations are located in the active site but are caused by mutations that disturb the correct packing of the protein."(6) As was described by these and many other experiments, conservation of the Thr206 in the active site is essential for correct catalysis of the enzyme. Mutations of the amino acids important to both the structure and function of the enzyme result in either complete loss of or reduced activity of aspartylglucosaminidase. As described previously, aspartlyglucoaminuria (AGU) is a lysosomal storage disease caused by incomplete processing and functioning of aspartylglucosaminidase.

I hope you have enjoyed viewing my web site. I hope the brief summary of the enzyme aspartylyglucosaminidase has helped you understand a little more about the importance of this enzyme. I would like to thank Carter E. Wahl for helping me obtain the documents necessary for completion of my site. I would also like to thank Brad Bass and Tony Vanden Bush for helping me with the computer business!!