Figure 1.
Structure of wild-type cardiac Troponin C.
The physiologically inactive binding site I contains
(yellow), while the active site II region contains
(tan). The locations of the mutants in this study are marked as colored bands, including E40 (black) V44 (red), L48 (green) and V79 (blue).
Figure 2.
Superposition of representative molecular dynamics snapshots for apo and holo mutant structures.
apo and holo states demonstrate the similar backbone structure for E40A (black) V44Q (red), L48Q (green), and V79Q (blue).
Table 1.
Ca2+ association rates.
Figure 3.
Calculated potential of mean force for Ca2+ approaching wild-type cardiac Troponin C site II binding region.
Potential of mean force [kcal/mol] is measured by distance between and Cγ of D76.
Table 2.
Summary of /Site II residue distances [Å] for mutants and wild type TnC.
Figure 4.
Simulated NMR order parameters.
Order parameters are provided for apo (dashed) and holo (solid) for LOF mutants V79Q (blue), E40A (black) b) and GOF mutants V44Q (red), L48Q (green). Site I and site II are located at approximately residues 28–38 and 67–76, respectively. revN:19.
Figure 5.
a) Helical lengths based on the entire MD simulation for apo structure are reported in red, and holo structure in blue. b) scaled representation of a).
Figure 6.
Distance between D67 and E76
of the apo-state structures.
Distances are reported in [Å] for E40A (black) V44Q (red), L48Q (green), and V79Q (blue).
Figure 7.
correlations for holo TnC mutants.
a) E40A b) V44Q c) L48Q d) V79Q. Positive correlations are reported in blue, negative correlations in red. Approximate secondary structure displayed along axes, with helices marked in black and
sheets in gray.
Table 3.
Summary of correlations in TnC mutants.
Figure 8.
interhelical angle for the holo state.
Angles reported in [deg] for E40A (black) V44Q (red), L48Q (green), and V79Q (blue) package.
Table 4.
Interhelical angle.