Crystal structure of IRS-2. (A) Overall 3-dimensional structure of IRS-2 in a cartoon representation. The central β-sheet A (magenta) and surrounding helices (cyan) are highlighted. The reactive center loop is cleaved in the relaxed (R-state) conformation of IRS-2 and forms the S4 β-strand (yellow) inserted into the β-sheet A; the termini generated by this proteolytic cleavage are marked by scissors. N- and C-termini of IRS-2 are labeled (N, C). (B) Stereo image showing a superposition of Cα traces of IRS-2 (red) with 2 homologous mammalian serpins in the R-state conformation. Antithrombin III (blue; 1ATT) and α-1-antichymotrypsin (green; 2ACH) display a high level of similarity to IRS-2 with regard to structural homology and inhibitory specificity, respectively.