Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the Keggin-type heteropolyoxotungstates (K7[PTi2W10O40]6H2O:PM-19) is a potent inhibitor of the replication of herpes simplex virus (HSV) both standard strain 169 and the thymidine kinase-defective strain YS-4C-1 in vitro and in vivo. HSV envelope protein, gD, is necessary for virus entry into the cells. Some cellular molecules, such as HVEM, were reported to act as cofactors during the viral entry step. We determined whether PM-19 prevents these interactions between HSV-gD and HVEM. These activities were investigated using the Ciphergen and BIACORE system. Using a protein chip, many kinds of gD-specific binding proteins were captured, but these proteins could not be identified. Several proteins in these gD-binding proteins were inhibited its interaction with gD due to the presence of PM-19. Using the BIACORE system, the affinity of PM-19 to gD was low, because PM-19 has no direct inactivation activity against the virion. The specific binding of HVEM to the gD was shown as KD of 1.1e-9. The affinity of PM-19 for HVEM was high (KD:2e-9). To determine the competitive binding, the PM-19 (10 microg/ml) and several concentrations of HVEM solution mixtures were injected over the gD-fixed sensor surface. Each binding signal was stable in the range of approximately 270-300 RU. In the case of the addition of PM-19 to HVEM solution, the binding signals were elevated by PM-19 dose dependently. These results suggest that the bindings of PM-19 to gD are not disturbed by the presence of HVEM. PM-19 prevents the interaction between HVEM and gD.
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PMID:Prevention of the interaction between HVEM, herpes virus entry mediator, and gD, HSV envelope protein, by a Keggin polyoxotungstate, PM-19. 1667 94