FIG. 2.

3D representations of targeted LEDGF/p75 residues. (A) The solution structure of the HDGF PWWP domain (Protein Data Base accession code 2B8A) is shown highlighting the residues that form its hydrophobic cavity (31, 39). (B) Cluster of basic Lys and Arg residues implicated in HDGF DNA binding (31). His-20 of the PHWP motif locates in this general vicinity; the extended N-terminal tail that harbors Arg-3 is not shown. (C) Remaining targeted residues. Ile-11, Pro-19, Val-28, Leu-40, Pro-41, and Ile-42 contribute to the hydrophobicity of the central cavity. Leu-10, Ile-11, Val-28, and Ile-42 are conserved among Tudor clan members (35), whereas Pro-19 is conserved among PWWP domain orthologs (39, 58). Note that Ile-11, Val-28, Leu-40, and Pro-41 are Val, Met, Tyr, and Gln in HDGF, respectively (Fig. 1B); the mutagenesis option in PyMOL (10) was used to model LEDGF/p75 residues at these positions. Residue numbers in panels A to C refer to LEDGF/p75; dark and light side-chain shadings indicate residues more toward the back and front of the page, respectively. Visible secondary structural elements are indicated as in Fig. 1B.