Destabilization of Zn2+ coordination in ADP‐ribose transferase (polymerizing) by 6‐nitroso‐1,2‐benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function

FEBS Letters

Kun, Ernest¹  Bauer, Pal I.¹  Hakam, Alaeddin¹  Mendeleyev, Jerome¹  Buki, Kalman G.¹ 

[1] Laboratory for Environmental Toxicology and Chemistry and the Octamer Research Foundation, Romberg Tiburon Centers, San Francisco State University, Tiburon, CA 94920, USA

关键词: Zinc finger;    6-Nitroso-1.2-benzopyrone;    ADP-ribose transferase;    ADPRT;    ADP-ribose transferase;    6-ABP;    6-amino-1;    2-benzopyrone;    6-NOBP;    6-nitroso-1;    2-benzopyrone;    6-NO2BP;    6-nitro-1;    2-benzopyrone;    M13ssDNA;    bacteriophage M13mp 18 single-stranded DNA;    MES;    2-(N-morpholino)ethanesulfonic acid;    GSH;    reduced glutathione;   

DOI  :  10.1016/0014-5793(91)81255-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

6-Nitroso- 1,2-benzopyrone, an oxidation product of 6-amino- 1,2-benzopyrone, binds to the DNA-recognizing domain of the ADP-ribose transferase protein and preferentially destabilizes Zn²⁺ from one of the two zinc finger polypeptide complexes present in the intact enzyme, as determined by the loss of 50% of ⁶⁵Zn²⁺ from the ⁶⁵Zn²⁺-isolated protein molecule, coincidental with the loss of 99% of enzymatic activity. The 50% zinc-deficient enzyme still binds to a DNA template. consisting of a 17-mer DNA primer annealed to M 13 positive strand, resulting in the blocking of DNA synthesis by the Klenow fragment of Pol I, Auto-poly-ADP-ribosylated ADP-ribose transferase, which is the probable physiological state of this protein in intact cells, does not bind to primer-template DNA and does not block DNA synthesis by the Klenow fragment. On the basis of this in vitro model it is proposed that molecules which inhibit or inactivate ADP-ribose transferase in intact cells can induce significant alteration in DNA structure and replication.

【 授权许可】

Unknown