Kinetic parameters and recognition of thymidine analogues with varying functional groups by thymidine phosphorylase

Akihiko Hatano, Aiko Harano, Yoshikatsu Takigawa, Yasuhiro Naramoto, Keisuke Toda, Yuuichi Nakagomi, Hideyuki Yamada

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Thymidine phosphorylase (TP, EC 2.4.2.4) recognized the structure of the substrate with high specificity, via both the base and the ribosyl moieties. The replacement of 3′-OH of thymidine markedly influenced its catalytic activity with TP. The conversion of pyrimidine nucleosides with modified base moieties to the corresponding 1-phosphate form was poor. The leaving group activity decreased with an increase in aromaticity of the pyrimidine base moiety, because of increased difficulty in polarizing the base by the amino acids local to the active site. The replacement of 3′ and 5′ functional groups tended to decrease the reaction rate and the percentage conversion with TP. In particular the ribosyl 3′ hydroxyl group was structurally important for the binding of the substrate by the enzyme. The kinetic assay clearly showed high Km and low Vmax values on replacing the 3′ hydroxyl group with hydrogen.

本文言語English
ページ(範囲)3866-3870
ページ数5
ジャーナルBioorganic and Medicinal Chemistry
16
7
DOI
出版ステータスPublished - 2008 4 1
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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