The basis for K-Ras4B binding specificity to protein farnesyl-transferase revealed by 2 Å resolution ternary complex structures Stephen B Long, Patrick.

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The basis for K-Ras4B binding specificity to protein farnesyl-transferase revealed by 2 Å resolution ternary complex structures Stephen B Long, Patrick J Casey, Lorena S Beese Structure Volume 8, Issue 2, Pages 209-222 (February 2000) DOI: 10.1016/S0969-2126(00)00096-4

Figure 1 Ribbon diagram of the overall structure of FTase complexed with an FPP analog (blue) and an 11-mer K-Ras-derived peptide substrate (green) shown as a stereo pair. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 2 The peptide molecules and FPP analog used in the crystal structures. (a) The peptide molecules in the ternary co-crystal structures compared with the C-terminal sequence of K-Ras4B. (b) Chemical structure of farnesyl diphosphate (FPP) compared with the FPP analog used in the ternary complexes. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 3 Stereoview of the active site 2Fo–Fc electron density calculated from 35–2.0 Å using phases from the final model and contoured at 1σ (blue) and 12σ (pink), indicating the location of the zinc ion. The map is drawn around the six C-terminal residues of the KKKSKTKCVIM, the zinc ion, and the zinc ligands. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 4 Ca1a2X binding. (a) Stereoview of the active site showing the peptide Ca1a2X motif (yellow) and FPP analog (purple). Protein residues within 4 Å of the Ca1a2X box and the buried solvent molecule (red sphere) that coordinates the C-terminal carboxylate are shown. The zinc ion is shown as a blue sphere. (b) Vertical slice of the molecular surface of the substrate-binding cavity of FTase, which binds the FPP analog (blue stick representation) and Ca1a2X portion of the peptide (yellow stick representation), shown as a stereo pair in approximately the same orientation as in (a). The surface is colored blue and yellow corresponding to the residues within van der Waals distance from the FPP analog and peptide substrate, respectively. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 5 Stereoview of the conformation of the entire KKKSKTKCVIM peptide (yellow). Hydrogen bonds made directly between the polybasic region of the peptide and FTase as well as intrapeptide hydrogen bonds are shown. Hydrogen bonds to backbone carbonyl oxygen atoms of FTase are indicated by green residue labels; those to FTase sidechains are indicated by black residue labels. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 6 β-Turn conformation of the Ca1a2X box of the peptide (yellow) bound to zinc-depleted FTase. The zinc-coordinated conformation (light blue) is superimposed. This view is approximately the same as that shown in Figure 4. Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)

Figure 7 Stereoview of Mn2+ bound to the FPP analog. An anomalous electron-density map calculated from 10–2.5 Å using phases from the final model and contoured at 3.5σ indicates the location of the Mn2+ ion. The protein ligands (gray) that interact with the diphosphate of FPP are shown forming hydrogen bonds with the FPP analog (brown). Structure 2000 8, 209-222DOI: (10.1016/S0969-2126(00)00096-4)