Role of protein X in the function of the mammalian pyruvate dehydrogenase complex

Gopalakrishnan, Subramaniam; Rahmatullah, Mohammed; Radke, Gary A.; Powers‐Greenwood, Susan L.; Roche, Thomas E.

doi:10.1016/0006-291x(89)92492-3

Cited by 46 publications

(35 citation statements)

References 19 publications

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“…In eukaryotic PDH complexes, an additional protein called the E3-binding protein (previously called "protein X" [37,100]) is required to tether the E3 subunit to the E2 core (64,117,176). The E3-binding protein (E3BP) is homologous to E2 subunits and includes a single lipoyl domain followed by a peripheral-subunit-binding domain (PSBD) and the catalytic domain (77,155).…”

Section: Lipoylated Complexesmentioning

confidence: 99%

“…Truncation of the lipoyl domain of yeast E3BP had little effect on PDH activity or on the formation of the complex (117), demonstrating that this domain is not important for E3BP function. Cleavage of a larger fragment from the N terminus of bovine E3BP resulted in inactive PDH complexes which lacked E3 subunits (64,176). In these experiments, proteolytic cleavage probably removed the PSBD as well as the lipoyl domain.…”

Section: Lipoylated Complexesmentioning

confidence: 99%

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Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

167

204

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SUMMARY Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.

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Section: Lipoylated Complexesmentioning

confidence: 99%

Section: Lipoylated Complexesmentioning

confidence: 99%

Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

167

204

View full text Add to dashboard Cite

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“…Section 1734 solely to indicate this fact. most eukaryotes is a lower abundance polypeptide termed protein X (17)(18)(19).…”

mentioning

confidence: 99%

“…Protein X from Ascaris suum, in contrast, does not contain a lipoyl domain (22). A characteristic common to all protein X subunits is that they can bind the E3 component with higher affinity than the E2 core, suggesting a possible function for this protein and prompting it being renamed the E3-binding protein (17)(18)(19)22). While it is clear that E3-binding proteins are present in animal and fungal PDCs, evidence for an E3-binding protein in plants is indirect and has not yet been confirmed (23).…”

mentioning

confidence: 99%

The Dihydrolipoamide S-Acetyltransferase Subunit of the Mitochondrial Pyruvate Dehydrogenase Complex from Maize Contains a Single Lipoyl Domain

Thelen¹,

Muszynski²,

David³

et al. 1999

Journal of Biological Chemistry

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Immunoanalysis of mitochondrial proteins from various plants, using a monoclonal antibody against the maize E2, revealed 50 -54-kDa cross-reacting polypeptides in all samples. A larger protein (76 kDa) was also recognized in an enriched pea mitochondrial PDC preparation, indicating two distinct E2s. The presence of a single lipoyl-domain E2 in Arabidopsis thaliana was confirmed by identifying a gene encoding a hypothetical protein with 62% amino acid identity to the maize homologue. These data suggest that all plant mitochondrial PDCs contain an E2 with a single lipoyl domain. Additionally, A. thaliana and other dicots possess a second E2, which contains two lipoyl domains and is only 33% identical at the amino acid level to the smaller isoform. The reason two distinct E2s exist in dicotyledon plants is uncertain, although the variability between these isoforms, particularly within the subunit-binding domain, suggests different roles in assembly and/or function of the plant mitochondrial PDC.

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“…It is not known whether the a and P subunits catalyze separate, partial reactions or whether af3 is the functional unit. Another possibility is that E1/3 plays a role in binding E1a to the E2 core (4,5), analogous to the role of protein X in anchoring E3 to the E2 core (6)(7)(8). Attempts to separate Ela and E113 with retention of enzymatic activity have been unsuccessful.…”

mentioning

confidence: 99%

Characterization of PDH beta 1, the structural gene for the pyruvate dehydrogenase beta subunit from Saccharomyces cerevisiae.

Miran

Lawson

Reed

1993

Proc. Natl. Acad. Sci. U.S.A.

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The gene encoding the pyruvate dehydrogenase (PDH) ( subunit (EIB) of the PDH complex from Saccharomyces cereviswae has been cloned, sequenced, disrupted, and expressed. Two overlapping DNA fragments were generated from a yeast genomic DNA library by the polymerase chain reaction with synthetic oligonucleotide primers based on amino acid sequences of the yeast and human Ell subunits.The DNA fragments were subcloned and sequenced. The composite sequence has an open reading frame of 1098 nucleotides encoding a putative presequence of 33 amino acid residues and a mature protein of 333 residues with a calculated

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Role of protein X in the function of the mammalian pyruvate dehydrogenase complex

Cited by 46 publications

References 19 publications

Lipoic Acid Metabolism in Microbial Pathogens

Lipoic Acid Metabolism in Microbial Pathogens

The Dihydrolipoamide S-Acetyltransferase Subunit of the Mitochondrial Pyruvate Dehydrogenase Complex from Maize Contains a Single Lipoyl Domain

Characterization of PDH beta 1, the structural gene for the pyruvate dehydrogenase beta subunit from Saccharomyces cerevisiae.

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