Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization
Figure 3
Conformational changes in cofactor (heparin) bound serpin (antithrombin) and residues involved in cofactor interaction. Heparin binding produces a series of conformational changes in antithrombin; extension of helix D by forming a 2 turn helix (P-helix) at the N-terminal end and a 1.5 turn extension of D-helix towards the C-terminal end. Moving of strand 3A and strand 5A and expulsion of reactive center loop leads to activated antithrombin. Given below are the basic residues in the heparin binding site that interact with the pentasaccharide are Lys-11 and Arg-13 in the N-terminal end; Arg-46 and Arg-47 in the A-helix; and Lys-114, Phe-121, Phe-122, Lys-125, and Arg-129 in the region of the D-helix. The figures were made by using antithrombin PDB (native 1E05; activated 1E03) files and swiss-prot PDB viewer.
