Effect of complex formation between Zn2+ ions and the anticancer drug mithramycin upon enzymatic activity of zinc(II)-dependent alcohol dehydrogenase.
Mithramycin (MTR), a member of the aureolic group of anticancer antibiotics, is a drug that supposedly acts via the inhibition of transcription. It binds to bivalent cations such as Mg(2+) and Zn(2+). In this paper, we report the association of MTR with Zn(2+), a biologically important bivalent cation whose coordination property leads to its important role as a cofactor in different enzymes and nucleosomal DNA-binding proteins. First, we have characterized the complex formation between MTR and Zn(2+) using spectroscopic methods. In the second part, we have examined the effect of the association of Zn(2+) with MTR on the enzymatic activity of a typical zinc(II)-dependent alcohol dehydrogenase (ADH) from yeast. Our data show that MTR forms a single complex with Zn(2+) in a mole ratio of 2:1 in terms of MTR:Zn(2+). We also observe a negative effect for the preincubation of ADH with MTR upon the enzymatic activity. These results indicate that MTR induced structural changes in the enzyme as a sequel to its complex formation with Zn(2+) present in the enzyme, thereby leading to a loss of enzymatic activity.
Das
Suman
S
Biophysics Division, Saha Institute of Nuclear Physics, Pin 700 064, Bidhan Nagar, Kolkata, India.
Devi
Pukhrambam Grihanjali
PG
Pal
Sudipta
S
Dasgupta
Dipak
D
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D008926:Plicamycin / Q000737:chemistry*; D013057:Spectrum Analysis; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D002413:Cations, Divalent; D000426:Alcohol Dehydrogenase; D015032:Zinc; D008926:Plicamycin