FIG 4.

Models of HIV-1 integrase containing wild-type and/or mutant amino acids in the intasome complex. (A) Surface view of the integrase G118R mutant catalytic site (colored by atom with carbons in orange) bound with dolutegravir (rendered in ball-and-stick format and colored by atom with carbons in white). (B) Ribbon-and-stick rendering of the integrase G118R mutant catalytic site (in green) bound with vDNA (in orange). Dolutegravir (as rendered in panel A) binds between the vDNA and tDNA catalytic loops and interacts with the catalytic Mg²⁺ (rendered in ball-and-stick format and colored in green). The tDNA and vDNA catalytic loops are highlighted in pink and magenta, respectively, and illustrate the locations of G118 and N144 (rendered in stick format) on each loop. Hydrogen bonding interactions between N144 with R263 and G118R with E92 are indicated by dashed yellow lines. (C) The integrase G118R mutant catalytic site (as rendered and oriented in panel B) bound to both vDNA and tDNA substrates (in orange). Hydrogen bonding interactions among G118R, the 3′ terminus of the tDNA, and the Mg²⁺ are indicated by dashed yellow lines. (D) Ribbon-and-stick rendering of the integrase catalytic site containing R263K (colored in magenta) and wild-type G118 bound with vDNA and tDNA substrates. DTG, dolutegravir; tDNA, host target DNA; vDNA, viral DNA.