Protein-Protein Interactions in the β-Oxidation Part of the Phenylacetate Utilization Pathway

Grishin, A.M.; Ajamian, Eunice; Zhang, Linhua; Rouiller, Isabelle; Bostina, Mihnea; Cygler, Mirosław

doi:10.1074/jbc.m112.388231

Cited by 13 publications

(14 citation statements)

References 40 publications

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“…Previous structural studies have characterized several enoyl-CoA hydratase/isomerase (ECH/ECI) including DsfA (PDB: 5FUS) from Burkholderia cenocepacia 24 , LiuC (PDB: 5JBX) from Myxococcus xanthus 25 , DmdD (PDB: 4IZB) from Ruegeria pomeroyi 26 , Echs1 (PDB: 1DCI) from Rattus norvegicus 27 , PaaF (PDB: 4FZW) from Escherichia coli 28 , RpfF (PDB: 3M6N) from Xcc and EchA8 (PDB: 3Q0G) from Mycobacterium tuberculosis 9 , 29 (Fig. 2a ).…”

Section: Resultsmentioning

confidence: 99%

Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis

Liu

Cheng

et al. 2018

Sci Rep

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DspI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, was proposed to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule in the pathogen Pseudomonas aeruginosa (P. aeruginosa). The present study provided a structural basis for the dehydration reaction mechanism of DspI during CDA synthesis. Structural analysis reveals that Glu126, Glu146, Cys127, Cys131 and Cys154 are important for its enzymatic function. Moreover, we show that the deletion of dspI results in a remarkable decreased in the pyoverdine production, flagella-dependent swarming motility, and biofilm dispersion as well as attenuated virulence in P. aeruginosa PA14. This study thus unravels the mechanism of DspI in diffusible signal factor (DSF) CDA biosynthesis, providing vital information for developing inhibitors that interfere with DSF associated pathogenicity in P. aeruginosa.Pseudomona aeruginosa (P. aeruginosa), as a common nosocomial gram-negative pathogenic bacterium, can inhabit a wide variety of ecological niches and infect diverse hosts. Owing to its intrinsic multi-drug resistance, P. aeruginosa is one of the leading causes of healthcare-associated infections, calling for effective treatments or agents with novel anti-infective mechanisms. In response to cell density or confinement to niches, P. aeruginosa adopts various signal molecules to mediate virulence factors biosynthesis and/or biofilm formation. Therefore, inhibiting these signaling pathways represents attractive strategies for developing novel therapeutics against P. aeruginosa infection 1-4 .In many pathogenic bacteria, quorum-sensing (QS) signaling is an important regulatory switch contributing to bacteria virulence and persistence 5 . By producing and releasing hormone-like chemical signal molecules involved in bacterial QS system, bacteria can communicate intercellularly to regulate a variety of physiological activities, such as motility, virulence, antibiotic production and biofilm dispersion. In the past few years, the diffusible signal factor (DSF) family has been disclosed as a new type of QS system signal that is common in gram-negative bacterial pathogens 6,7 . The first identified DSF family molecule cis-11-methyl-2-dodecenoic acid, was found in the plant pathogen Xanthomonas campestris pv. campestris (X.cc) 8 , which regulates many biological functions including cell growth, biofilm dispersion and virulence 9 . Cis-2-decenoic acid (CDA) is a new member of the DSF family that was found in P. aeruginosa and functions as an auto-inducer for biofilm dispersion 10,11 . Additionally, as an inter-kingdom signaling molecule, CDA also regulates the biofilm formation and dispersion in a number of other pathogens [12][13][14][15] .So far, multiple DSF family molecules have been detected in various pathogens 7 . A particular group of particular enoyl-coenzyme A (CoA) hydratase/isomerases includes RpfF from X.cc, which appears to be the key enzyme in DSF biosynthesis 7,[16][17][18][19][20][21] . In P. aeruginosa, the gene PA0745 ...

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Section: Resultsmentioning

confidence: 99%

Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis

Liu

Cheng

et al. 2018

Sci Rep

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“…Methods similar to those described above were used to identify stable complexes among enzymes PaaA, PaaB, PaaC, PaaF, PaaG, PaaH, PaaJ, and PaaZ. In numerous co-expression experiments of up to seven Paa enzymes in a single cell, only one stable complex was identified, that between PaaF and PaaG [ 33 ].…”

Section: The Upper Part Of the Pathwaymentioning

confidence: 99%

“…The crystal structure of the PaaF-PaaG complex was determined at 2.5 Å resolution [ 33 ]. Both proteins possess a crotonase fold and, as is common for proteins with this fold, they assemble into homotrimeric discs ( Figure 3 A,B).…”

Section: The Upper Part Of the Pathwaymentioning

confidence: 99%

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Structural Organization of Enzymes of the Phenylacetate Catabolic Hybrid Pathway

Grishin

Cygler

2015

Biology

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Aromatic compounds are the second most abundant class of molecules on the earth and frequent environmental pollutants. They are difficult to metabolize due to an inert chemical structure, and of all living organisms, only microbes have evolved biochemical pathways that can open an aromatic ring and catabolize thus formed organic molecules. In bacterial genomes, the phenylacetate (PA) utilization pathway is abundant and represents the central route for degradation of a variety of organic compounds, whose degradation reactions converge at this pathway. The PA pathway is a hybrid pathway and combines the dual features of aerobic metabolism, i.e., usage of both oxygen to open the aromatic ring and of anaerobic metabolism—coenzyme A derivatization of PA. This allows the degradation process to be adapted to fluctuating oxygen conditions. In this review we focus on the structural and functional aspects of enzymes and their complexes involved in the PA degradation by the catabolic hybrid pathway. We discuss the ability of the central PaaABCE monooxygenase to reversibly oxygenate PA, the controlling mechanisms of epoxide concentration by the pathway enzymes, and the similarity of the PA utilization pathway to the benzoate utilization Box pathway and β-oxidation of fatty acids.

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“…Another geneblock co-occurrence we find in our study is that of paaF and paaG, in 12 out of 23 species in which any components of the paa orthoblock occur. The products of these two genes form the FaaGH complex, another stable complex which catalyzes consecutive steps in the phenylacetate degradation pathway, and it was hypothesized that the proximity of the two proteins in a complex provides a fitness advantage [11]. Another use of the event-driven method is the reconstruction of ancestral gene blocks along the evolutionary tree.…”

Section: Conservation Of Gene Blocks and Relationship To Functionmentioning

confidence: 99%

An event-driven approach for studying gene block evolution in bacteria

2015

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Motivation: Gene blocks are genes co-located on the chromosome. In many cases, gene blocks are conserved between bacterial species, sometimes as operons, when genes are co-transcribed. The conservation is rarely absolute: gene loss, gain, duplication, block splitting and block fusion are frequently observed. An open question in bacterial molecular evolution is that of the formation and breakup of gene blocks, for which several models have been proposed. These models, however, are not generally applicable to all types of gene blocks, and consequently cannot be used to broadly compare and study gene block evolution. To address this problem, we introduce an event-based method for tracking gene block evolution in bacteria.Results: We show here that the evolution of gene blocks in proteobacteria can be described by a small set of events. Those include the insertion of genes into, or the splitting of genes out of a gene block, gene loss, and gene duplication. We show how the event-based method of gene block evolution allows us to determine the evolutionary rateand may be used to trace the ancestral states of their formation. We conclude that the event-based method can be used to help us understand the formation of these important bacterial genomic structures.Availability and implementation: The software is available under GPLv3 license on http://github.com/reamdc1/gene_block_evolution.git. Supplementary online material: http://iddo-friedberg.net/operon-evolutionContact: i.friedberg@miamioh.eduSupplementary information: Supplementary data are available at Bioinformatics online.

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Protein-Protein Interactions in the β-Oxidation Part of the Phenylacetate Utilization Pathway

Cited by 13 publications

References 40 publications

Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis

Structural and functional studies on Pseudomonas aeruginosa DspI: implications for its role in DSF biosynthesis

Structural Organization of Enzymes of the Phenylacetate Catabolic Hybrid Pathway

An event-driven approach for studying gene block evolution in bacteria

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