Figure 3.  Y181C mutation decreases hydrophobic interactions with an NNRTI.  The figure shows a comparison of the NNRTI binding pockets of wild-type HIV-1 RT and the Y181C mutant in a complex with an NNRTI (TIBO).  The backbone of the p66 subunit of the wild-type RT is shown in red; the amino acid side chains are blue.  The loop of wild-type p51 that carries E138 is shown in blue.  The backbone and side chains of Y181C are gray.  The position of TIBO in the wild-type structure is shown in green; the position of TIBO in the Y181C mutant is shown in gold.  In contrast to the side chain of a tyrosine at position 181, which interacts with TIBO and has a defined position in the crystal structure, the side chain of a cysteine at position 181 does not interact with TIBO and is delocalized; this is shown as a cone, which represents plausible positions for the side chain.  The loss of this hydrophobic interaction is the basis for the resistance of RTs carrying the Y181C mutation.