1887

Abstract

SUMMARY

Two TK acyclovir-resistant variants of herpes simplex virus (HSV) (S1 and Tr7) and one TK BVdU-resistant variant (B3) induce abnormal thymidine kinases with impaired ability to phosphorylate the drugs used in their isolation. These enzymes have been purified and their properties compared with those of the wild-type () parent, SC16. The enzyme induced by S1 differed markedly from the other three in both its responses to salt and to pH. B3 TK recognized the enzyme’s natural substrates, thymidine, deoxycytidine, dTMP and ATP as well as the enzyme. In contrast, Tr7 and S1 TKs failed to bind deoxycytidine and bind thymidine less well than Tr7 and S1 TKs had affinities for dTMP similar to those of B3 and the enzymes. ATP binding to , Tr7 and B3 enzymes was similar but this substrate bound only weakly to S1 TK. Each mutant displayed a characteristically distinct pattern of affinities for a range of nucleoside analogue substrates, suggesting that they will show some cross-resistance to drugs which have a similar mechanism of action to acyclovir and BVdU.

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1983-03-01
2022-01-23
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