A theoretical study of glucosamine synthase. Part I. Molecular mechanics calculations on substrate binding.
Glucosamine synthase transfers the gamma-amino group of glutamine to fructose, producing 1-glucosamine which is the key constituent of bacterial and fungal cell walls. In this study, model calculations were performed on substrate binding to the enzyme active site. Two models of the active site of glucosamine synthase were proposed, which assume two different sequences of aminoacids, Cys-Gly-Ile and Cys-Ala-Cys, the first one being the N-terminal sequence of the Escherichia coli enzyme. Several initial geometries were assumed for these tripeptides, the energy was then optimized by means of molecular mechanics. It has been found that the structure which is both energy optimal and satisfies the assumed cysteine sulphur arrangement consists of combinations of C7eq and C7ax conformations of single residues. Molecular mechanics calculations were then performed on glutamine and D-fructose-6-phosphate, which are the substrates of the enzymatic catalysis, and on their complex with the enzyme glutamine-binding site. The spatial configuration of the compounds under study, which is optimal as far as the reaction path is concerned, also turned out to be an energy minimum.
Tempczyk
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Institute of Chemistry, University of Gdańsk, Poland.
Tarnowska
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Liwo
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D000409:Alanine; D000595:Amino Acid Sequence; D003545:Cysteine; D005636:Fructosephosphates / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006860:Hydrogen Bonding; D008433:Mathematics; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
D005636:Fructosephosphates; C027618:fructose-6-phosphate; D005974:Glutamate-Ammonia Ligase; D003545:Cysteine; D000409:Alanine