FIG. 5.

Detailed views comparing wild-type SEPSECS crystal structure and mutated amino acids modeled in the SEPSECS crystal structure that cause either early onset (red) or late onset (yellow) disease (71). Hydrogen bonds (dotted green lines), pyridoxal-5-phosphate substrate (cyan), tRNA (orange), and H₂O (blue) are shown. The helices (H), beta-sheets (β), amino acids, and nucleotides involved in hydrogen bond networks or that are part of the active catalytic domain are labeled. Crystal structures for T325S and Y334C SEPSECS mutants are available and in the panels with these mutations an overlay of wild type (gray) and mutant (cyan) is shown (73). The effect of these mutations is described in detail in section SEPSECS in main text. The model was generated by using the phyre2 web portal, which predicts and analyzes protein structures based on homology/analogy recognition to solve protein crystal structures (51). The figures were generated with MacPyMOL Molecular Graphics System, Schrödinger, LLC. Color images are available online.