title: Studies of cadmium binding to hexokinase: structural and functional implications.
abstract: The interaction between cadmium and yeast hexokinase was studied. Cadmium produces changes in the aggregation state of the protein and large structures with a large molecular mass were formed. This phenomenon occurs without large modifications to the secondary structure. During this change the enzyme maintains a high level of activity in the monomer as well as in aggregate form. This implies that the enzyme function is not greatly affected by the change and it maintains its active sites without significant modifications. According to kinetic measurements with both glucose and ATP as a variable substrate, cadmium causes a mixed-type inhibition with a main uncompetitive component. Binding experiments show that the protein presents negative cooperative binding with cadmium at various temperatures (298, 303 and 313 K) and a progressive loss in metal union with concentration depending on the temperature. The total union percentage decreases as the metal concentration increases. This is probably due to the aggregation process, which affects the binding sites for the metal and also for the substrate. Labile interactions are more persistent than specific interactions in accordance with the solvation parameter.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Olmo
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Blanco
authors.forename: César
authors.initials: C
authors.lastname: Teijón
authors.forename: Jesús
authors.initials: J
authors.lastname: Miguel del Socorro
authors.forename: Jose María
authors.initials: JM
authors.lastname: Teijón
mesh_terms: D002104:Cadmium / Q000378:metabolism*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006593:Hexokinase / Q000378:metabolism*; D007700:Kinetics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000201:enzymology
chemical_list: D002104:Cadmium; D006593:Hexokinase