Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate.
Metabolic transformation of AZTp4A by Ap4A hydrolase regenerates AZT triphosphate.
复制标题
Ap4A 水解酶对 AZTp4A 的代谢转化可再生 AZT 三磷酸。
DOI：
10.1016/s0166-3542(03)00003-2
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发表时间：
2003
影响因子：
7.6
通讯作者：
London,RobertE
中科院分区：
文献类型：
--
作者：
Pitcher3rd,WayneH;Kirby,ThomasW;DeRose,EugeneF;London,RobertE
The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZTp4A. In the present study, we report that AZTp4A is an excellent substrate for the enzyme Ap4A hydrolase (asymmetrical dinucleoside tetraphosphatase, EC 3.6.1.17), an enzyme that is widely distributed in many cell types. Progress of the reaction has been monitored by31P NMR, and it was found that hydrolysis results in the production of AZTTP:ATP in a 7:1 ratio. The AZTp4A was also hydrolyzed at a rate 1.8-fold more rapidly than Ap4A. Spectrophotometric assays yielded Michaelis constants of 2.35 and 0.71μM for Ap4A and AZTp4A, respectively. It, therefore, appears that Ap4A hydrolase can play a useful role in the regeneration of the AZTTP, the active form of AZT, for the inhibition of HIV RT.
