Binding of ellipticine to beta-lactoglobulin. A physico-chemical study of the specific interaction of an antitumor drug with a transport protein.
The unprotonated form of the anti-tumor alkaloid ellipticine binds to beta-lactoglobulins A and B from bovine milk with an affinity constant of 7 +/- 3 x 10(5) M-1. There is one binding site/dimeric protein molecule (the stable form at medium pH). The attachment site is not the beta-barrel nor the hydrophobic site identified as the retinol site in beta-lactoglobulin but a domain located at the interface of the two monomeric units where the ligand lies close to Trp61 of both polypeptide chains. The positive binding enthalpy observed in temperature-jump relaxation experiments is overcome by a strong entropy increase, tentatively thought to result from water release at the binding domain. Accordingly, desolvation is assumed to be the rate-determining step in the process of ellipticine binding.
Dodin
G
G
Institut de Topologie et de Dynamique des Systèmes de l'Université Paris, France.
Andrieux
M
M
al Kabbani
H
H
D000818:Animals; D002417:Cattle; D004611:Ellipticines / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D007782:Lactoglobulins / Q000378:metabolism*; D008433:Mathematics; D008892:Milk; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
D004611:Ellipticines; D007782:Lactoglobulins; C034192:ellipticine