FIG. 2.

(A) Superimposition of the X-ray structures of the wild-type and the V36M variant NS3 protease domains in a complex with the NS4A cofactor. The Cα atom traces of both the wild-type (in purple) and the V36M variant (in blue) proteases are shown as lines. Residue 36 is highlighted with a stick model (Val³⁶ in green and Met³⁶ in yellow). (B and C) Close-up view of the side chains of residue 36 and the other key residues in the wild-type NS3-4A protease (B) and the V36M variant protease (C). The catalytic triad (His⁵⁷, Asp⁸¹, and Ser¹³⁹) is shown in red. Residue 36 is highlighted either in green (Val³⁶ of the wild type) or in yellow (Met³⁶ of the V36M variant). Other key NS3 protease residues (Phe⁴³, Ile⁶⁴, and Trp⁸⁵) are shown in blue, and Ile²⁵ of the NS4A cofactor is shown in cyan. (D) Close-up view of the H bond between residues Thr⁵⁴ and Leu⁴⁴ in the wild-type NS3-4A protease. Thr⁵⁴ of the C1 β strand (in cyan) forms an H bond (shown as a dashed line) with the main-chain carbonyl of Leu⁴⁴ of the B1 β strand (in green). The locations of Phe⁴³ (in green) and Val³⁶ (in orange) are also shown. Nitrogen atoms are colored in blue, and oxygen atoms are colored in red.