Fig. 1

Reference alignment of sequences. All sequences are aligned to the AHo system with other numbering systems shown above each indicated sequence. A Comparison of structures from commercial mAb-based molecules with Trp at AHo position 41 and crystal structures in the PDB. The Trp at position 41 in the Aho numbering system falls at 35 or 35A in the Kabat system (red highlighted column) even though this residue is structurally identical across the different mAb crystal structures (Trp41 shown as sticks and circled in Red; PDB 4X7T (Jensen et al. 2015), green; PDB 5SX5 (Sickmier et al. 2016), grey; PDB 6B3S (Bagchi et al. 2018), blue). B Comparison of structures from commercial mAb-based molecules with Met at position 136 in AHo numbering and crystal structures in the PDB. The Met at AHo position 136 is numbered 100A, 100E, 100G, or 100M in the Kabat system across the different molecules (red highlighted column) even though crystal structures indicate the position of this Met is highly homologous across the structures (Met136 shown as sticks and circled in Red; PDB 6AL4 (Teplyakov et al. 2018), light blue; PDB 5WUV (Lee et al. 2017), light green; PDB 6UMH (Garces et al. 2020), light cyan; PDB 3GIZ (Du et al. 2009), light gray)