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Figure 4.
Figure 4. Ca^2+-Induced Conformational Changes in the
Active Site Region of Calpain and Proposed Activation
Mechanism(A) DI and II of inactive human m calpain (Strobl et
al., 2000). The ribbon presentation is colored pink, with the
side chains of three critical residues (equivalent to μ R104,
W298, and E333) colored orange. DI and II are rotated 5°
relative to each other, and C105 and H262 are 10.5 Å
apart.(B) DI of μI-II (blue) was overlapped onto DI from m
calpain (pink) using the program Align (Cohen, 1997). The gold
sphere indicates the Ca^2+ ion.(C) Exposure of the Ca^2+ binding
site in DII (cyan) resulting from attraction of the E333 side
chain by R104 from DI.(D) R104-E333 double salt bridge stereo
view.(E) Overlap of DII from μI-II (cyan) onto DII from m
calpain (pink) showing the loops that coordinate the second
Ca^2+. Note: a discrepancy in the m calpain structure around
G295 results in a discontinuity in that peptide loop.(F) Stereo
view of the hydrophobic pocket formed by Ca^2+ binding to
DII.(G) Ca^2+ bound μI-II, showing the arrangement of the Ca^2+
ions relative to the active site cleft. This is a 90°
rotation of the view in Figure 2A.
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