Drug PF-3450074 binds to part of the CPSF6-binding interface in HIV-1 CA^N.

<p>(<b>A</b>) Superposition of HIV-1 CA^N:PF-3450074 structure (pdb: 2XDE) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002896#ppat.1002896-Blair1" target="_blank">[38]</a> on HIV-1 CA^N:CPSF6_313–327 using secondary structure matching of the HIV-1 CA^N domains. Drug PF-3450074 is shown in cyan, CPSF6_313–327 in yellow. The three CPSF6 residues that fill the centre of the channel in HIV-1 are indicated. One of the phenyl rings in PF-3450074 superposes almost exactly with the phenyl ring of F321 in CPSF6_313–327. (<b>B</b>) Crystal structure of HIV-1 CA^N:PF-3450074 (pdb: 2XDE) showing residues involved in binding to CPSF6 (green sticks). The yellow sphere represents a water molecule involved in a water-mediated interaction in the complex. (<b>C</b>) ITC of PF-3450074 against wild type and mutant HIV-1 CA^Ns. (<b>D</b>) Titration of 1 mM CPSF6_313–327 into 80 µM HIV-1 CA^N was carried out in the absence or presence of 100 µM PF-3450074 (‘control’ and ‘+ drug’ respectively). PF-3450074 completely inhibits binding of CPSF6_313–327 to HIV-1 CA^N.