Fig. 6
From: Crystal structure and substrate-induced activation of ADAMTS13
Electrostatic potential at the molecular surface of ADAMTS13 MDTCS (MP through to Spacer). The charged surface representation of MDTCS is presented in the “front” view as in Fig. 4 b (negative charges—red; positive charges—blue). Domains are labelled above. The active-site and the disintegrin-like (Dis), cysteine (Cys)-rich and Spacer domain exosites are circled. The L1D loop in the Dis domain that was not fully resolved in the DTCS structure is highlighted, and also the L2D loop. Together, these loops provide the interaction site for reciprocally charged Von Willebrand factor (VWF) residues 1615–1622. The peptide Tyr1605-Asp1622 is shown. The distance from the metalloprotease (MP) domain active-site to Arg349 in the Dis domain is 26 Å, which matches the distance from the Tyr1605-Met1606 scissile bond to Asp1614 that interacts with Arg349. The Spacer domain exosite involving Arg660, Tyr661, and Tyr665 has been reported to interact with the C-terminal CUB domains of ADAMTS13. We propose that the Spacer domain makes a hydrophobic interaction with Leu1664, Val1665, and Leu1666 with an adjacent surface hydrophobic patch (green) centered around Ile611
