Fig. 4

In silico analysis of pyruvate dehydrogenase complex E3 p.P87S variant. Cartoon representation of homodimeric PDC E3 crystallographic structure (PDB entry 6I4T; one monomer represented in blue, the other in grey). Flavin adenine dinucleotide (FAD) cofactor in yellow sticks. Right panel, zoom-in on the location of the P87S substitution. P87 is located in an α-helix which contains the active site cysteine residues C80 and C85. Substitution of P by S will likely affect the helix structure and disturb the proximity between the active site disulphide and the FAD cofactor. Structural model of PDC-E1 p.R302H variant was obtained by loading the structure of WT PDC-E3 (PDB entry 6IT4) into Pymol and applying the mutagenesis tool to generate all possible rotamers of the substituting amino acid side chain