Figure 1

Location of F25 in the sequence and structure of hPGK1 and the biological significance of the mutations analyzed in this study. (A) Sequence of the hPGK1 protein (UniProt and Gene ID are indicated). The position of F25 is highlighted. (B) Structural location of F25 in two different conformations (open and closed) of hPGK1. The open conformation (PDB code 2XE7) is shown in green and closed conformation (PDB code 2X13) is shown in blue. These structures were reported in¹⁴. The location of 3-PG, ADP and Mg²⁺ is also indicated as well the two domains of the protein. Please note that the conformational transition from open to closed conformation causes changes in F25 as well as in the ligands 3-PG and ADP. (C) Frequency of naturally-occurring mutations in hPGK1. Data were retrieved from ClinVar and COSMIC databases, and mutations were categorized in three meaningful sets: Cavity-making (Cavity set, in dark red), Strain-inducing (Strain set, orange) or Glycine-affecting (Glycine set, dark yellow). The percentage of mutations belonging to either of these three sets which are buried in the structure is indicated in red. Details on the statistical classification and the identity of these mutations are found in Table S2.