Structural and mechanistic insights into the bifunctional enzyme isocitrate dehydrogenase kinase/phosphatase AceK

Zheng, Jimin; Yates, Susan P.; Jia, Zongchao

doi:10.1098/rstb.2011.0426

Cited by 26 publications

(23 citation statements)

References 50 publications

(89 reference statements)

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“…Moreover, DiO slightly induced the expression of RER_17540 and RER_17550, which encode the beta and the alpha subunits of acetyl-CoA carboxylase, respectively. These differing conclusions from Sabirova's study might be due to the distinct properties of the carbon source used as a control in the two studies (Zheng et al 2012) or diverse metabolic profiles of the two strains.…”

Section: Discussionmentioning

confidence: 72%

Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons

Laczi

Kis

Horváth

et al. 2015

Appl Microbiol Biotechnol

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Rhodococcus erythropolis PR4 is able to degrade diesel oil, normal-, iso-and cycloparaffins and aromatic compounds. The complete DNA content of the strain was previously sequenced and numerous oxygenase genes were identified. In order to identify the key elements participating in biodegradation of various hydrocarbons, we performed a comparative whole transcriptome analysis of cells grown on hexadecane, diesel oil and acetate. The transcriptomic data for the most prominent genes were validated by RT-qPCR. The expression of two genes coding for alkane-1-monooxygenase enzymes was highly upregulated in the presence of hydrocarbon substrates. The transcription of eight phylogenetically diverse cytochrome P450 (cyp) genes was upregulated in the presence of diesel oil. The transcript levels of various oxygenase genes were determined in cells grown in an artificial mixture, containing hexadecane, cycloparaffin and aromatic compounds and six cyp genes were induced by this hydrocarbon mixture. Five of them were not upregulated by linear and branched hydrocarbons. The expression of fatty acid synthase I genes was downregulated by hydrocarbon substrates, indicating the utilization of external alkanes for fatty acid synthesis. Moreover, the transcription of genes involved in siderophore synthesis, iron transport and exopolysaccharide biosynthesis was also upregulated, indicating their important role in hydrocarbon metabolism. Based on the results, complex metabolic response profiles were established for cells grown on various hydrocarbons. Our results represent a functional annotation of a rhodococcal genome, provide deeper insight into molecular events in diesel/hydrocarbon utilization and suggest novel target genes for environmental monitoring projects.

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Section: Discussionmentioning

confidence: 72%

Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons

Laczi

Kis

Horváth

et al. 2015

Appl Microbiol Biotechnol

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“…It is a bifunctional enzyme which uniquely presents both kinase and phosphatase activities. AceK represents a more extreme case of kinase diversity compared with the eukaryotic protein kinases (ePKs) superfamily [2]. With the opposing activities at the same highly adaptable active site, AceK regulates the action of isocitrate dehydrogenase (ICDH) and acts as the metabolic switch between the Krebs cycle and the glyoxylate bypass in response to nutrient availability [3].…”

Section: Introductionmentioning

confidence: 99%

Unique Kinase Catalytic Mechanism of AceK with a Single Magnesium Ion

Zheng

Tan

et al. 2013

PLoS ONE

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Isocitrate dehydrogenase kinase/phosphatase (AceK) is the founding member of the protein phosphorylation system in prokaryotes. Based on the novel and unique structural characteristics of AceK recently uncovered, we sought to understand its kinase reaction mechanism, along with other features involved in the phosphotransfer process. Herein we report density functional theory QM calculations of the mechanism of the phosphotransfer reaction catalysed by AceK. The transition states located by the QM calculations indicate that the phosphorylation reaction, catalysed by AceK, follows a dissociative mechanism with Asp457 serving as the catalytic base to accept the proton delivered by the substrate. Our results also revealed that AceK prefers a single Mg2+-containing active site in the phosphotransfer reaction. The catalytic roles of conserved residues in the active site are discussed.

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“…For a long time, it was believed that the role of phosphorylation in the regulation of bacterial cell processes was limited to the phosphorelay of twocomponent systems, the phosphotransfer system in the uptake of sugars (Stülke & Hillen, 1998) and serine phosphorylation of the catabolite control protein A (ccpA) (Fujita, 2009), and in the regulation of the isocitrate dehydrogenase by the bifunctional AceK kinase/phosphatase controlling the entry into the glyoxylate shunt (Zheng & Jia, 2010;Zheng, Yates, & Jia, 2012). However, the introduction and application of MS-based methods (Gerber, Rush, Stemman, Kirschner, & Gygi, 2003;Macek, Mann, & Olsen, 2009;Vill en & Gygi, 2008;Wang, Pan, & Tao, 2014) for the global identification of eubacterial and archaeal phosphoproteomes demonstrated that this view was too narrow (Macek & Mijakovic, 2011;Mijakovic & Macek, 2012).…”

Section: Protein Phosphorylationmentioning

confidence: 99%

Bacterial Electron Transfer Chains Primed by Proteomics

Wessels¹,

Almeida²,

Kartal³

et al. 2016

Advances in Bacterial Electron Transport Systems and Their Regulation

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Electron transport phosphorylation is the central mechanism for most prokaryotic species to harvest energy released in the respiration of their substrates as ATP. Microorganisms have evolved incredible variations on this principle, most of these we perhaps do not know, considering that only a fraction of the microbial richness is known. Besides these variations, microbial species may show substantial versatility in using respiratory systems. In connection herewith, regulatory mechanisms control the expression of these respiratory enzyme systems and their assembly at the translational and posttranslational levels, to optimally accommodate changes in the supply of their energy substrates. Here, we present an overview of methods and techniques from the field of proteomics to explore bacterial electron transfer chains and their regulation at levels ranging from the whole organism down to the Ångstrom scales of protein structures. From the survey of the literature on this subject, it is concluded that proteomics, indeed, has substantially contributed to our comprehending of bacterial respiratory mechanisms, often in elegant combinations with genetic and biochemical approaches. However, we also note that advanced proteomics offers a wealth of opportunities, which have not been exploited at all, or at best underexploited in hypothesis-driving and hypothesis-driven research on bacterial bioenergetics. Examples obtained from the related area of mitochondrial oxidative phosphorylation research, where the application of advanced proteomics is more common, may illustrate these opportunities.

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Structural and mechanistic insights into the bifunctional enzyme isocitrate dehydrogenase kinase/phosphatase AceK

Cited by 26 publications

References 50 publications

Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons

Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons

Unique Kinase Catalytic Mechanism of AceK with a Single Magnesium Ion

Bacterial Electron Transfer Chains Primed by Proteomics

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