(A) The GBV-C genome, including the 5′ and 3′ non-translated regions (NTR), is shown. The structural genes include the envelope proteins E1 and E2, and the non-structural genes include NS2, NS3, NS4A, NS4B, NS5A, and NS5B. The regions coding for NS3, NS3/4A, and NS3/4A/4B that were cloned are shown. The relative position of the NS3 serine protease catalytic serine residue (S137) is shown. (B) Comparison of the HCV and GBV-C serine protease catalytic triad. Partial protease sequences of HCV1b (CON1 sequence), HCV1a (H77 sequence), HCV2a (JFH-1 sequence), are compared with the GBV-C AY196904 sequence. The catalytic triad consists of histidine 56, aspartic acid 79, and serine 137 (blue letters, underlined and in bold). Histidine 56 and serine 137 are expressed in similar peptide contexts in both HCV and GBV-C (blue letters). The GBV-C residues are numbered from the experimentally determined amino terminus of GBV-C NS3. (C) Comparison of the known cleavage recognition sequences of the HCV and GBV-C NS3 serine proteases. *Adapted from [42]. **Adapted from [17], [18].