Identification of putative Ca2+-binding sites in ADAMTS13 metalloprotease domain by homology modeling. (A-C) The ADAMTS13 metalloprotease domain was homology-modeled using the crystal structure of adamalysin II (1IAG). Structures are depicted in cartoon format. Zn2+ ion and 3 active-site His residues are shown in blue. (A) Site 1 predicted to involve E83, D173, C281, and D284 is shown in red. Ca2+ ion also present in adamalysin II crystal structure in a homologous site is shown as a red sphere. (B) Putative Site 2 is in proximity to Site 1 (shown in red) and may involve residues N162, E164, D165, D166, and D168, which are highlighted in green. (C) Putative Site 3 is located on the opposite side of the metalloprotease domain to Site 1 and Site 2 (shown in red and green, respectively) and lies adjacent to the active-site cleft. Site 3 may involve residues D182, E184, D187, and E212, which are shown in purple.
