Figure 5. Cartoon showing the excision reaction. As shown in the upper diagram on the left, excision requires that the end of the primer strand (which is blocked by an NRTI) be bound at the N site (see Figure 3). In the second diagram, an ATP binds to RT in a fashion that the beta and gamma phosphates of the ATP bind in the position normally occupied by pyrophosphate. In a reaction that is analogous to polymerization run in reverse, the phosphate linking the last two nucleotides on the primer strand is joined to the gamma phosphate of ATP, generating a dinucleotide tetraphosphate (lower left). However, if the NRTI that has been incorporated into the primer strand is a ddNTP, then it can be translocated from the N to the P site (right diagram). If high levels of dNTPs are present, the appropriate incoming dNTP binds, forming a closed complex, which prevents excision. The long azido group of AZT interferes with the formation of a stable closed complex, which gives an AZTMP-terminated primer better access to the N site, where it can be excised.
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