Structures of the Human Pyruvate Dehydrogenase Complex Cores: A Highly Conserved Catalytic Center with Flexible N-Terminal Domains

Xuekui Yu, Yasuaki Hiromasa, Hua Tsen, James K. Stoops, Thomas E. Roche, Z. Hong Zhou

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 Å 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.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
JournalStructure
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 8 2008

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Structures of the Human Pyruvate Dehydrogenase Complex Cores: A Highly Conserved Catalytic Center with Flexible N-Terminal Domains'. Together they form a unique fingerprint.

  • Cite this