Figure 1.

The crystal structure of human glycosylated AGT. A, the N-terminal tail sequence of AGT, indicating the renin and ACE cleavage sites, the glycosylation site, and the conserved disulfide bond. B, the structure of AGT is shown as a cartoon. The serpin template is in gray, and helix A (hA) is in marine with the A-sheet (sA) in light blue and the disordered RCL in red dashes. The Ang I segment is in magenta, and the following amino-tail is in green with the scissile bond shown as magenta and green spheres. Cysteine 18 in the amino tail forms a disulfide bond with cysteine 138 of the CD-loop (brown). The glycan attached to Asn¹⁴ is shown as green sticks. The segment from Glu²⁰ to Pro²⁹ (dashed, pale green) is disordered in the structure and modeled for illustration. Helix H (hH) is in red, and helix G (hG) is in wheat color. C, surface representation of the main body of AGT, with the extra N terminus (residues 1–63) shown in a cartoon representation. The Ang I peptide is mainly stabilized by hydrophobic interactions with the main body. Residues Ile⁵, Phe⁸, Leu¹⁰, Val¹¹, and Ile¹² (shown as sticks) form hydrophobic interactions with residues in the CD-loop (Val¹³¹, Pro¹³², and Trp¹³³ as brown surface), helix A (Leu⁶⁸, Met⁷², Leu⁷⁶, and Phe⁷⁹ as marine surface), and helix D (hD; Leu¹⁴² and Val¹⁴⁷ as cyan surface). The scissile bond (Leu¹⁰–Val¹¹) is buried in the hydrophobic cavity.