Fig. 3. Structural analysis of CaM thioamide variants. Top Left: potential hydrogen bonding interactions for stabilization observed in Val^S ₁₃₆ and Glu^S ₁₃₉ substitutions. Right: neutral (Val^S ₁₄₂ and Ala^S ₁₄₇) and destabilizing (Tyr^S ₁₃₈, Glu^S ₁₄₀, and Phe^S ₁₄₁) substitutions. Destabilization of CaM by Phe^S ₁₄₁ and Tyr^S ₁₃₈ and may be due to disruption in the packing of the helix. Glu^S ₁₄₀ disrupts hydrogen bond acceptance without making a compensatory hydrogen bond donor interaction. Increased C O···N distance (3.1 Å) in the turn of the helix at Val^S ₁₄₂ may allow for better accommodation of the thioamide sulfur. Ala^S ₁₄₇ is the penultimate C-terminal residue and only serves as a hydrogen bond donor. Structures rendered from PDB entry ; 1QX5 chains D (yellow) and R (green) and from PDB entry ; 1CFD (orange, only N-terminal region shown). ^34,35 .