Supplementary Figure 4: Groove-binding peptides approach Pep2-8 and EGF(A) in a similar fashion as the native P'-helix. | Nature Structural & Molecular Biology

Supplementary Figure 4: Groove-binding peptides approach Pep2-8 and EGF(A) in a similar fashion as the native P'-helix.

From: Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists

Supplementary Figure 4

(a) The Pro4 residue of Pep1 is in the same location as Pro155 of the native P'-helix and contacts the side chains of residues Trp6 and Tyr9 of Pep2-8. Analogous contacts are observed for Pep3 (not shown). (b) The structurally analogous PCSK9 P'-helix Pro155 contacts EGF(A) Leu298 in the PCSK9/EGF(A) complex (PDB 2W2M). (c) Cyclic peptides Pep1 (green-yellow) and Pep3 (brown) are closely similar in sequence and structure when bound to PCSK9 and display a residue (Arg2, Phe2) close to the volume occupied by Ser153 in the native P’-helix (Ser153-Ile154-Pro155 in white).

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