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Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex
- Source :
- Biochemistry, vol 57, iss 16
- Publication Year :
- 2018
- Publisher :
- eScholarship, University of California, 2018.
-
Abstract
- Pyruvate dehydrogenase complex (PDC) is a large multienzyme complex that catalyzes the irreversible conversion of pyruvate to acetyl-coenzyme A with reduction of NAD+. Distinctive from PDCs in lower forms of life, in mammalian PDC, dihydrolipoyl acetyltransferase (E2; E2p in PDC) and dihydrolipoamide dehydrogenase binding protein (E3BP) combine to form a complex that plays a central role in the organization, regulation, and integration of catalytic reactions of PDC. However, the atomic structure and organization of the mammalian E2p/E3BP heterocomplex are unknown. Here, we report the structure of the recombinant dodecahedral core formed by the C-terminal inner-core/catalytic (IC) domain of human E2p determined at 3.1 Å resolution by cryo electron microscopy (cryoEM). The structure of the N-terminal fragment and four other surface areas of the human E2p IC domain exhibit significant differences from those of the other E2 crystal structures, which may have implications for the integration of E3BP in mammals. This structure also allowed us to obtain a homology model for the highly homologous IC domain of E3BP. Analysis of the interactions of human E2p or E3BP with their adjacent IC domains in the dodecahedron provides new insights into the organization of the E2p/E3BP heterocomplex and suggests a potential contribution by E3BP to catalysis in mammalian PDC.
- Subjects :
- 0301 basic medicine
Biochemistry & Molecular Biology
Stereochemistry
Cryo-electron microscopy
Protein Conformation
Pyruvate Dehydrogenase Complex
macromolecular substances
Medical Biochemistry and Metabolomics
Dihydrolipoyllysine-Residue Acetyltransferase
Biochemistry
Article
Catalysis
03 medical and health sciences
Medicinal and Biomolecular Chemistry
Protein structure
Rare Diseases
Oxidoreductase
Catalytic Domain
Humans
Pyruvate Dehydrogenase (Lipoamide)
Amino Acid Sequence
Binding site
Dihydrolipoyl transacetylase
Dihydrolipoamide Dehydrogenase
chemistry.chemical_classification
Dihydrolipoamide dehydrogenase
Binding Sites
030102 biochemistry & molecular biology
Cryoelectron Microscopy
hemic and immune systems
Pyruvate dehydrogenase complex
030104 developmental biology
chemistry
NAD+ kinase
Biochemistry and Cell Biology
Carrier Proteins
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Biochemistry, vol 57, iss 16
- Accession number :
- edsair.doi.dedup.....2998dd009556add6846605bdbe509ee1