Dolutegravir Interactions with HIV-1 Integrase-DNA: Structural Rationale for Drug Resistance and Dissociation Kinetics
Figure 2
Structural models of HIV-1 integrase with U5 LTR DNA and (A, B) raltegravir, (C) elvitegravir or (D) dolutegravir.
For raltegravir, the terminal 3′ adenylate is depicted in 2 distinct conformations: panel 2A shows the published conformer and panel 2B shows an alternative conformer that is also consistent with the observed electron density. Raltegravir, elvitegravir and dolutegravir are in stick representation with carbon, nitrogen, oxygen, fluorine and chlorine atoms colored gray, blue, red, cyan and green, respectively. A select subset of amino acids and nucleotides is depicted and labeled with residue type and number (numbering schemes as listed in Figure S1); all residues are in stick representation with carbon atoms colored by secondary structure/chain and nitrogen and oxygen atoms colored blue and red, respectively. The Mg2+ ions are represented as small yellow spheres with coordinate bonds to the inhibitors depicted as dashed yellow lines.