Molecular models of the ADAMTS13 S1′ subsite. (A) Model of the ADAMTS13 MP-Dis domains based on the crystal structures of the corresponding domains from ADAMTS1, -4, and -5. The active site histidines are shown in dark blue and the bound Zn²⁺ is shown as a sphere. Enlarged boxed area shows the active site in more detail. The S1′pocket that accommodates the P1′ residues in VWF (Met1606) is circled in white. The VR3B(I) region is shown in red with visible residues labeled. (B) Model as in panel A in the same orientation except that the VR3B(I) region (D252-P256) in ADAMTS13 MP domain has been substituted for the corresponding 5 residues in ADAMTS1. Changing these amino acids appreciably alters the shape/depth of the S1′ pocket.