Download MendeleyStructures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains
Yu, X., Hiromasa, Y., Tsen, H., Stoops, J.K., Roche, T.E., Zhou, Z.H.(2008) Structure 16: 104-114
- PubMed: 18184588
- DOI: https://doi.org/10.1016/j.str.2007.10.024
- Primary Citation of Related Structures:
3B8K - PubMed Abstract:
Dihydrolipoyl acetyltransferase (E2) is the central component of pyruvate dehydrogenase complex (PDC), which converts pyruvate to acetyl-CoA. Structural comparison by cryo-electron microscopy (cryo-EM) of the human full-length and truncated E2 (tE2) cores revealed flexible linkers emanating from the edges of trimers of the internal catalytic domains. Using the secondary structure constraints revealed in our 8 A cryo-EM reconstruction and the prokaryotic tE2 atomic structure as a template, we derived a pseudo atomic model of human tE2. The active sites are conserved between prokaryotic tE2 and human tE2. However, marked structural differences are apparent in the hairpin domain and in the N-terminal helix connected to the flexible linker. These permutations away from the catalytic center likely impart structures needed to integrate a second component into the inner core and provide a sturdy base for the linker that holds the pyruvate dehydrogenase for access by the E2-bound regulatory kinase/phosphatase components in humans.
Organizational Affiliation:
Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
