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Figure 1
Overall structure of hDHTKD1. (a) A schematic of hDHTKD1 domain organization, indicating disease-causing missense mutations with arrows. (b) Structure of the hDHTKD1 homodimer, where one subunit is coloured according to the domain organization from panel (a) and the other subunit is coloured grey. ThDP co-factors and Mg2+ ions are shown as sticks and spheres, respectively. (c) Sites of missense mutations are shown as black spheres on one hDHTKD1 protomer [same view as panel (b)]. (d) Structural superposition of hDHTKD1, ecOGDH (PDB code 2jgd) and msOGDH (PDB code 6r2b; Wagner et al., 2019BB58) highlighting their different inter-domain linkers (coloured purple, blue and light brown, respectively). (e) A magnified view of the dotted box in panel (d), showing how the hDHTKD1 inter-domain linker (purple) packs against two loop regions (black). Binding positions for the allosteric effectors AMP in the ecOGDH structure (PDB code 2jgd) and acetyl-CoA in the msOGDH structure (PDB code 2y0p; Wagner et al., 2011BB57) are shown as blue and brown meshes, respectively. (f) Overall architectures of the hDHTKD1 homodimer (left), the human (PDHA–PDHB)2 heterotetramer (middle, PDB code 1ni4; Ciszak et al., 2003BB10) and the human (BCKDHA–BCKDHB)2 heterotetramer (right, PDB code 1dtw; Ævarsson et al., 2000BB2) are shown. hDHTKD1 homodimer has a larger volume because of the insertions coloured red.

IUCrJ
Volume 7| Part 4| July 2020| Pages 693-706
ISSN: 2052-2525
https://doi.org/10.1107/S205225252000696X