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  • 标题:Regulation of the reverse transcriptase of human immunodeficiency virus type 1 by dNTPs.
  • 本地全文:下载
  • 作者:A B West ; T M Roberts ; R D Kolodner
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1992
  • 卷号:89
  • 期号:20
  • 页码:9720-9724
  • DOI:10.1073/pnas.89.20.9720
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Reverse transcriptase (RNA-directed DNA polymerase, EC 2.7.7.49 ) of human immunodeficiency virus type 1 has been examined with respect to the steady-state kinetics of polymerization of dNTPs into product DNA. With dNTPs as variable substrate, the kinetics of polymerization deviated from standard Michaelis-Menten kinetics. Substrate inhibition was observed at high substrate concentrations and negative cooperativity was seen at lower substrate concentrations. Examination of incorporation of substrate dNMPs in the presence of nucleotides not complementing the template demonstrated that dNTPs may act as noncompetitive inhibitors, as well as substrate. The Ki of the enzyme for dNTPs was 104 microM. A working model is presented that accounts for the substrate inhibition. In this model, the reverse transcriptase is a multisubunit holoenzyme, where noncompetitive inhibition is mediated by one subunit binding nucleotide and down-regulating the enzymatically active 64-kDa subunit. With additional assumptions, this model can accommodate the negative cooperativity observed.
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