Gene and subunit organization of bacterial pyruvate dehydrogenase complexes

Neveling, Ute; Bringer-Meyer, Stephanie; Sahm, Hermann

doi:10.1016/s0167-4838(98)00080-6

Cited by 35 publications

(32 citation statements)

References 32 publications

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“…E2 and E3 are components of the PDH multienzyme complex, which catalyzes the irreversible oxidative decarboxylation of pyruvate to acetyl-coenzyme A. PDH complexes of Gram-positive bacteria have a core of 60 E2 subunits with icosahedral symmetry (41). Besides its role in oxidative metabolism, the E2 subunit appears to have DNA binding activity (42,43).…”

Section: Discussionmentioning

confidence: 99%

A Uracil-DNA Glycosylase Inhibitor Encoded by a Non-uracil Containing Viral DNA

Serrano‐Heras

Salas

Bravo

2006

Journal of Biological Chemistry

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Uracil-DNA glycosylase (UDG) is an enzyme involved in the base excision repair pathway. It specifically removes uracil from both single-stranded and double-stranded DNA. The genome of the Bacillus subtilis phage 29 is a linear double-stranded DNA with a terminal protein covalently linked at each 5-end. Replication of 29 DNA starts by a protein-priming mechanism and generates intermediates that have long stretches of single-stranded DNA. By using in vivo chemical cross-linking and affinity chromatography techniques, we found that UDG is a cellular target for the early viral protein p56. Addition of purified protein p56 to B. subtilis extracts inhibited the endogenous UDG activity. Moreover, extracts from 29-infected cells were deficient in UDG activity. We suggested that inhibition of the cellular UDG is a defense mechanism developed by 29 to prevent the action of the base excision repair pathway if uracil residues arise in their replicative intermediates. Protein p56 is the first example of a UDG inhibitor encoded by a nonuracil-containing viral DNA.Uracil in DNA may arise from spontaneous deamination of cytosine and from the occasional use of dUTP instead of dTTP during DNA replication. Hydrolytic deamination of cytosine generates G:U mismatches that cause G:C to A:T transition mutations. To maintain the genome integrity, most prokaryotic and eukaryotic cells rapidly eliminate uracil from DNA by the base excision repair (BER) 2 pathway, which is initiated by the uracil-DNA glycosylase (UDG) enzyme. UDGs have an unusually broad phylogenetic distribution. Some DNA viruses, such as herpesviruses and poxviruses, also encode a UDG activity, whereas the human immunodeficiency virus, type 1, packages cellular UDG (UNG2 enzyme) into virus particles. In these instances, the UDG activity appears to have an important role in virus replication (1).The UDG enzyme hydrolyzes the N-glycosidic bond between the uracil residue and the deoxyribose sugar of the DNA backbone, generating an apurinic-apyrimidinic (AP) site. The first UDG activity reported was purified from Escherichia coli cells (2). Since then, enzymes highly homologous to the archetypal E. coli UDG have been identified in numerous organisms, including human cells (Family-1 UDGs) (3). Studies on substrate specificity showed that Family-1 UDGs efficiently remove uracil residues from both single-stranded and double-stranded DNAs, often with preference for the single-stranded substrates (4, 5). The AP site generated by the UDG enzyme is further recognized by an AP endonuclease, which cleaves the phosphodiester bond of the DNA backbone 5Ј to the AP site. Several AP endonucleases are active not only on double-stranded DNAs but also on singlestranded DNAs (6 -8). Further repair can be accomplished via two pathways that involve different subsets of enzymes and result in replacement of one (short patch pathway) or more (long patch pathway) nucleotides (9).Over the course of evolution, bacteriophages have developed unique proteins that bind to and inactivate critical cellula...

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Section: Discussionmentioning

confidence: 99%

A Uracil-DNA Glycosylase Inhibitor Encoded by a Non-uracil Containing Viral DNA

Serrano‐Heras

Salas

Bravo

2006

Journal of Biological Chemistry

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“…Efforts to understand genes important for sporulation in B. subtilis revealed that subunits of the PDH and KDH complexes are required for this process (47,52). Bacillus subtilis contains the PDH E1␣, E1␤, E2, and E3 subunits (encoded by pdhA, pdhB, pdhC, and pdhD, respectively) (157). pdhA is refractory to disruption and thus appears to be essential for cell growth, while disruptions of the individual genes pdhB, pdhC, and pdhD all result in sporulation defects (60).…”

Section: Gram-positive Bacteriamentioning

confidence: 99%

Lipoic Acid Metabolism in Microbial Pathogens

Spalding

Prigge

2010

Microbiol Mol Biol Rev

165

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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“…These accessory proteins are apparently lacking in bacterial PDH where regulation occurs through allosteric mechanisms and product inhibition (54). The E1 protein of PDH from mitochondria and from Gram-positive bacteria is composed of two different subunits (E1␣ and E1␤), which form an ␣ 2 ␤ 2 heterotetramer (52,55). In contrast, the E1 protein in many Gram-negative bacteria is organized as a homodimer of translationally fused ␣ and ␤ subunits ((␣␤) 2 ) (54,55).…”

Section: Proteomic Studies Reveal An Anaerobic Response In Euglenamentioning

confidence: 99%

“…The E1 protein of PDH from mitochondria and from Gram-positive bacteria is composed of two different subunits (E1␣ and E1␤), which form an ␣ 2 ␤ 2 heterotetramer (52,55). In contrast, the E1 protein in many Gram-negative bacteria is organized as a homodimer of translationally fused ␣ and ␤ subunits ((␣␤) 2 ) (54,55). Our present data from Euglena indicate that its mitochondrial PDH has a typical E1␣, E1␤, E2, E3 subunit organization as in other eukaryotes.…”

Section: Proteomic Studies Reveal An Anaerobic Response In Euglenamentioning

confidence: 99%

Euglena gracilis Rhodoquinone:Ubiquinone Ratio and Mitochondrial Proteome Differ under Aerobic and Anaerobic Conditions

Hoffmeister¹,

Klei

Rotte

et al. 2004

Journal of Biological Chemistry

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Euglena gracilis cells grown under aerobic and anaerobic conditions were compared for their whole cell rhodoquinone and ubiquinone content and for major protein spots contained in isolated mitochondria as assayed by two-dimensional gel electrophoresis and mass spectrometry sequencing. Anaerobically grown cells had higher rhodoquinone levels than aerobically grown cells in agreement with earlier findings indicating the need for fumarate reductase activity in anaerobic wax ester fermentation in Euglena. Microsequencing revealed components of complex III and complex IV of the respiratory chain and the E1␤ subunit of pyruvate dehydrogenase to be present in mitochondria of aerobically grown cells but lacking in mitochondria from anaerobically grown cells. No proteins were identified as specific to mitochondria from anaerobically grown cells. cDNAs for the E1␣, E2, and E3 subunits of mitochondrial pyruvate dehydrogenase were cloned and shown to be differentially expressed under aerobic and anaerobic conditions. Their expression patterns differed from that of mitochondrial pyruvate:NADP ؉ oxidoreductase, the N-terminal domain of which is pyruvate:ferredoxin oxidoreductase, an enzyme otherwise typical of hydrogenosomes, hydrogen-producing forms of mitochondria found among anaerobic protists. The Euglena mitochondrion is thus a long sought intermediate that unites biochemical properties of aerobic and anaerobic mitochondria and hydrogenosomes because it contains both pyruvate:ferredoxin oxidoreductase and rhodoquinone typical of hydrogenosomes and anaerobic mitochondria as well as pyruvate dehydrogenase and ubiquinone typical of aerobic mitochondria. Our data show that under aerobic conditions Euglena mitochondria are prepared for anaerobic function and furthermore suggest that the ancestor of mitochondria was a facultative anaerobe, segments of whose physiology have been preserved in the Euglena lineage.

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Gene and subunit organization of bacterial pyruvate dehydrogenase complexes

Cited by 35 publications

References 32 publications

A Uracil-DNA Glycosylase Inhibitor Encoded by a Non-uracil Containing Viral DNA

A Uracil-DNA Glycosylase Inhibitor Encoded by a Non-uracil Containing Viral DNA

Lipoic Acid Metabolism in Microbial Pathogens

Euglena gracilis Rhodoquinone:Ubiquinone Ratio and Mitochondrial Proteome Differ under Aerobic and Anaerobic Conditions

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