Crystal structure of human plasma β-FXIIa. (A) Stereo ribbon diagram (cyan) of β-FXIIa in complex with covalent compound 1 inhibitor in “standard” orientation. Compound 1 is shown in green sticks. The side chains of key β-FXIIa residues are shown as magenta sticks: His57, Asp102, and Ser195 of the catalytic triads, Asp189 at the base of the S1 specificity pocket. The side chains of N-glycosylated Asn74 and NacGlc-disaccharide are shown in cyan sticks. Some surface loops discussed in the text are labeled and shown in pink. The heavy chain remnant of β-FXIIa is shown in red. Hydrogen bonds are indicated by black dotted lines. (B) The structure of β-FXIIa in complex with noncovalent benzamidine inhibitor is represented as in panel A. Six disulfide bonds are indicated and are shown in yellow. (C) Superposition of the β-FXIIa (benzamidine [magenta] and β-FXIIa) compound 1 (cyan) crystal structures. The catalytic domains are superimposed by aligning the Cα atoms of residues 16-244 and are presented as cartoon diagrams. Benzamidine (orange), compound 1 (green), and residues of the catalytic triad are shown in a stick representation.