Structural and Functional Analyses of the Human PDH Complex Suggest a `Division-of-Labor` Mechanism by Local E1 and E3 Clusters (Structure)

Structural and functional analyses of human PDHc reveals an uneven subunit distribution in the core and periphery suggesting a `division-of-labor` mechanism of local E2-E1 and E3BP-E3 clusters during the multi-step reaction. Substrate CoA is found to modulate the conformational landscape and inter-domain coupling of PDHc extending the MRC mechanism.