Modifying human thymidylate kinase to potentiate azidothymidine activation

被引：55

作者：

Brundiers, R

Lavie, A

Veit, T

Reinstein, J

Schlichting, I

Ostermann, N

Goody, RS

Konrad, M

机构：

[1] Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44227 Dortmund, Germany

[2] Max Planck Inst Biophys Chem, Dept Mol Genet, D-37070 Gottingen, Germany

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1999年 / 274卷 / 50期

关键词：

D O I：

10.1074/jbc.274.50.35289

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Based on the knowledge of the crystal structures of yeast and Escherichia coli thymidylate kinases (TmpKs) and the observation that TmpK from E. coli can phosphorylate azidothymidine monophosphate (AZT-MP) much more efficiently than either the yeast or the highly homologous human enzyme, we have engineered yeast and human TmpKs to obtain enzymes that have dramatically improved AZT-MP phosphorylation properties. These modified enzymes have properties that make them attractive candidates for gene therapeutic approaches to potentiating the action of AZT as an inhibitor of human immunodeficiency virus (HIV) replication. In particular, insertion of the lid domain of the bacterial TmpK into the human enzyme results in a pronounced change of the acceptance of AZT-MP such that it is now phosphorylated even faster than TMP.

引用

页码：35289 / 35292

页数：4

共 16 条

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