|Coutinho, Pedro - IOWA STATE UNIVERSITY|
|Reilly, Peter - IOWA STATE UNIVERSITY|
Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 31, 1995
Publication Date: N/A
Interpretive Summary: Glucoamylase is an enzyme that converts starch to produce glucose. This enzyme has an important role in the fructose industry. Extensive efforts are underway to find modified versions of this enzyme with different properties that would be commercially useful. In order to facilitate this research effort, we have started a series of computational studies to further our understanding of the activity of glucoamylase. These simulations mimic the binding of small molecules to the enzyme's active site. The computational results are in good agreement with reported experimental work. This information should lead to a more detailed understanding of the functions of this enzyme and should help direct future experimental efforts.
Technical Abstract: Glucoamylase is an enzyme that hydrolyzes starch to glucose. The enzyme is an important component of the corn fructose sweeteners industry. Extensive efforts are underway to find variants of this enzyme with different catalytic properties, including modified thermal stability and pH activity. Several studies have been undertaken to define the substrate specificity of the enzyme, and classical screening and genetic manipulation experiments have also been reported to isolate mutants with different catalytic properties. In this work we report on efforts to simulate the binding of small substrates into the active site of this enzyme. Several monosaccharides, disaccharides, and known inhibitors have been docked using Monte Carlo-based AutoDock 2.1 (Scripps Research Institute, La Jolla, CA). The computational results compared favorably with published crystallography results and kinetically-determined binding constant for several of the docked molecules. This information should lead to a more detailed understanding of the catalytic functions of this enzyme and should help direct future mutagenesis studies.