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Figure 2
Substrate binding pocket of hDHTKD1. (a) A view of the active site from the hDHTKD1 structure (pink ribbon) bound with ThDP (sticks, white carbon atoms) and Mg2+ (yellow), overlaid with the ecOGDH structure in the apo form (light blue ribbon; PDB code 2jgd), to highlight structural differences in various loop regions. (b) The same hDHTKD1 active-site view as in panel (a), overlaid with msOGDH structures in complex with the first post-de­carboxyl­ation intermediate (cyan ribbons for proteins, sticks with cyan carbon atoms for ligands; PDB code 3zht) and second post-de­carboxyl­ation intermediate (blue ribbons for proteins, sticks with blue carbon atoms for ligands; PDB code 3zhu). (c) The hDHTKD1 substrate pocket is lined by residues from both subunits of the homodimer (pink and blue lines). Overlaid in this pocket is the putative 2OA ligand (pink sticks) modelled in our density (Fig. S6) and the post-de­carboxyl­ation intermediates (cyan sticks) bound to the msOGDH structures. (d) The hDHTKD1–metabolite interactome as determined by MIDAS. hDHTKD1 significantly depleted 2OA and α-oxoisovalerate, and enriched dAMP and dGMP. The cutoff for significance was p < 0.05 and q < 0.1.

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