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Table 2 HIV-1 RT Amino Acid Residues Composing the Putative dNTP-Binding Sites and the Locations of NRTI-<br />

Resistance Mutations (see also [12])<br />

dNTP-Binding Site Nucleoside <strong>Drug</strong>-Resistance Mutation Site<br />

Residue Location Mutation Location Possible Effects References<br />

Asp110 β6 Met41Leu αA template binding 55<br />

Asp113 β6-αC loop Ile50Thr β2 unclear 154<br />

Try115 αC Lys65Arg β3–β4 template binding 154<br />

Phe116 αC Asp67Asn β3–β4 template binding 155<br />

Gln151 β8-αE Thr69Asp β3–β4 template binding 156<br />

Phe160 αE Lys70Arg β3–β4 template binding 155<br />

Asp185 β9–β10 Leu74Val β4 template binding 8<br />

Asp186 β9–β10 Val75Thr β4 template binding 163<br />

Lys219 β11 Glu89Gly β5 dsDNA binding 157<br />

Tyr115Phe αC dNTP binding 170<br />

Ile135Thr β7–β8 unclear 158,159<br />

Gln151Met β8-αE dNTP binding<br />

Met184Val, Ile β9–β10 dNTP-binding/fidelity 154,160,161<br />

Thr215Tyr, Phe,<br />

Cys<br />

β11 indirect effect/dNTP<br />

binding<br />

155,162<br />

Lys219Gln β11 dNTP binding 155<br />

Page 52<br />

site can accommodate both the normal dNTP substrates and dideoxynucleoside analogs. The majority of<br />

mutations that confer resistance to NRTIs are not located at the dNTP-binding site; however, they<br />

appear to influence the geometry of the dNTP-binding site indirectly in a way that permits RT to<br />

discriminate between a normal dNTP and a modified nucleoside triphosphate (see discussion in the next<br />

section).<br />

http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_52.html (1 of 2) [4/5/2004 4:49:26 PM]

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