The aspartate aminotransferase-like domain of Firmicutes MocR transcriptional regulators

Milano, Teresa; Contestabile, Roberto; Presti, Alessandra Lo; Ciccozzi, Massimo; Pascarella, Stefano

doi:10.1016/j.compbiolchem.2015.05.003

Cited by 16 publications

(25 citation statements)

References 43 publications

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“…Two clades are most populated: GabR appears to belong to one of these clades (clade1) while the three fold type I structures 1XOM, 1WST and 2EGY are most similar to MocR‐TFs of clade2. A comparison among the sequences of the three clades pointed several clade‐specific residues possibly related to functional diversification . However, these findings do not solve the questions about the evolutionary origin of the MocR family.…”

Section: Evolution Of Mocr‐tfsmentioning

confidence: 72%

“…Currently, an exhaustive structural and evolutionary analysis of the MocR family is missing, although a few studies have been published with the aim to shed light on the evolutionary relationships between MocR and PLP‐dependent enzymes . An exhaustive sequence comparison between the AAT‐like domain of a set of MocR regulators and fold type I PLP‐dependent enzymes with known three‐dimensional structure have suggested that AAT‐like MocR domains are most similar to the human kynurenine aminotransferase II homologue from Pyrococcus horikoshii (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1XOM), the multiple substrate aminotransferase from Thermococcus profundus (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1WST), and 2‐aminoadipate aminotransferase from Thermus thermophilus (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=2EGY) .…”

Section: Evolution Of Mocr‐tfsmentioning

confidence: 99%

“…An exhaustive sequence comparison between the AAT‐like domain of a set of MocR regulators and fold type I PLP‐dependent enzymes with known three‐dimensional structure have suggested that AAT‐like MocR domains are most similar to the human kynurenine aminotransferase II homologue from Pyrococcus horikoshii (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1XOM), the multiple substrate aminotransferase from Thermococcus profundus (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=1WST), and 2‐aminoadipate aminotransferase from Thermus thermophilus (PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=2EGY) . More recently, sequence alignment and phylogenetic analyses of the AAT‐like domains of Firmicutes MocR‐TFs suggested that at least three different clades can be distinguished within the Firmicutes AAT‐like domain population . Two clades are most populated: GabR appears to belong to one of these clades (clade1) while the three fold type I structures 1XOM, 1WST and 2EGY are most similar to MocR‐TFs of clade2.…”

Section: Evolution Of Mocr‐tfsmentioning

confidence: 99%

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The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

et al. 2018

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Many biological functions played by current proteins were not created by evolution from scratch, rather they were obtained combining already available protein scaffolds. This is the case of MocR-like bacterial transcription factors (MocR-TFs), a subclass of GntR transcription regulators, whose structure is the outcome of the fusion between DNA-binding proteins and pyridoxal 5'-phosphate (PLP)-dependent enzymes. The resultant chimeras can count on the properties of both protein classes, i.e. the capability to recognize specific DNA sequences and to bind PLP and amino-compounds; it is the modulation of such binding properties to confer to MocR-TFs chimeras the ability to interact with effector molecules and DNA so as to regulate transcription. MocR-TFs control different metabolic processes involving vitamin B and amino acids, which are canonical ligands of PLP-dependent enzymes. However, MocR-TFs are also implicated in the metabolism of compounds that are not substrates of PLP-dependent enzymes, such as rhizopine and ectoine. Genomic analyses show that MocR-TFs are widespread among eubacteria, implying an essential role in their metabolism and highlighting the scarcity of our knowledge on these important players in microbial metabolism. Although MocR-TFs have been discovered 15 years ago, the research activity on these transcriptional regulators has only recently intensified, producing a wealth of information that needs to be brought back to general principles. This is the main task of this review, which reports and analyses the available information concerning MocR-TFs functional role, structural features, interaction with effector molecules and the characteristics of DNA transcriptional factor-binding sites of MocR-based regulatory systems.

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Section: Evolution Of Mocr‐tfsmentioning

confidence: 72%

Section: Evolution Of Mocr‐tfsmentioning

confidence: 99%

Section: Evolution Of Mocr‐tfsmentioning

confidence: 99%

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The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

et al. 2018

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“…Still another MocR family member, TauR, was found to activate taurine-dependent tpa expression (6). Five of 54 putative GntR family transcriptional regulators in S. meliloti can be classified into the MocR subfamily (24), and none of those proteins has been characterized previously. Unlike other MocR family transcriptional regulators that were shown to activate their targets, we discovered that EhuR negatively regulates the transcription of ehuABCDeutABCDE.…”

Section: Discussionmentioning

confidence: 99%

Negative Regulation of Ectoine Uptake and Catabolism in Sinorhizobium meliloti: Characterization of the EhuR Gene

Cai

Zhang

et al. 2017

J Bacteriol

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Ectoine has osmoprotective effects on Sinorhizobium meliloti that differ from its effects in other bacteria. Ectoine does not accumulate in S. meliloti cells; instead, it is degraded. The products of the ehuABCD-eutABCDE operon were previously discovered to be responsible for the uptake and catabolism of ectoine in S. meliloti. However, the mechanism by which ectoine is involved in the regulation of the ehuABCD-eutABCDE operon remains unclear. The ehuR gene, which is upstream of and oriented in the same direction as the ehuABCD-eutABCDE operon, encodes a member of the MocR/GntR family of transcriptional regulators. Quantitative reverse transcription-PCR and promoter-lacZ reporter fusion experiments revealed that EhuR represses transcription of the ehuABCD-eutABCDE operon, but this repression is inhibited in the presence of ectoine. Electrophoretic mobility shift assays and DNase I footprinting assays revealed that EhuR bound specifically to the DNA regions overlapping the Ϫ35 region of the ehuA promoter and the ϩ1 region of the ehuR promoter. Surface plasmon resonance assays further demonstrated direct interactions between EhuR and the two promoters, although EhuR was found to have higher affinity for the ehuA promoter than for the ehuR promoter. In vitro, DNA binding by EhuR could be directly inhibited by a degradation product of ectoine. Our work demonstrates that EhuR is an important negative transcriptional regulator involved in the regulation of ectoine uptake and catabolism and is likely regulated by one or more end products of ectoine catabolism.IMPORTANCE Sinorhizobium meliloti is an important soil bacterium that displays symbiotic interactions with legume hosts. Ectoine serves as a key osmoprotectant for S. meliloti. However, ectoine does not accumulate in the cells; rather, it is degraded. In this study, we characterized the transcriptional regulation of the operon responsible for ectoine uptake and catabolism in S. meliloti. We identified and characterized the transcription repressor EhuR, which is the first MocR/GntR family member found to be involved in the regulation of compatible solute uptake and catabolism. More importantly, we demonstrated for the first time that an ectoine catabolic end product could modulate EhuR DNA-binding activity. Therefore, this work provides new insights into the unique mechanism of ectoine-induced osmoprotection in S. meliloti.KEYWORDS Sinorhizobium meliloti, EhuR, MocR, ectoine, transcriptional regulator S inorhizobium meliloti is a soil bacterium that can be found either free-living or on the roots of leguminous plants. The ability to adapt to changes in the osmolality of the external soil environment is of vital importance for the growth and survival of soil bacteria, and ectoine serves as a key osmoprotectant for S. meliloti (1). Unlike many other bacteria, however, S. meliloti does not produce ectoine. Therefore, other soil

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“…They possess a conserved structural organization with an N-terminal DNA-reading head containing a winged helix-turn-helix DNA-binding motif that is connected via a flexible linker region to a large carboxy-terminal effectorbinding/dimerization domain. This latter domain is structurally related to aminotransferases of type-I fold (Edayathumangalam et al, 2013;Milano et al, 2015;Suvorova and Rodionov, 2016). It frequently contains a covalently bound pyridoxal-5'-phosphate (PLP) co-factor (attached to a Lys-residue) but MocR/GabR-type regulators do not perform a full aminotransferase enzyme reaction (Edayathumangalam et al, 2013;Okuda et al, 2015a,b;Takenaka et al, 2015;Park et al, 2017;Wu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of ectoine catabolism in response to multiple metabolic and environmental cues

Schulz

Hermann

Freibert

et al. 2017

Environmental Microbiology

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Ectoine and hydroxyectoine are effective microbial osmostress protectants, but can also serve as versatile nutrients for bacteria. We have studied the genetic regulation of ectoine and hydroxyectoine import and catabolism in the marine Roseobacter species Ruegeria pomeroyi and identified three transcriptional regulators involved in these processes: the GabR/MocR-type repressor EnuR, the feast and famine-type regulator AsnC and the two-component system NtrYX. The corresponding genes are widely associated with ectoine and hydroxyectoine uptake and catabolic gene clusters (enuR, asnC), and with microorganisms predicted to consume ectoines (ntrYX). EnuR contains a covalently bound pyridoxal-5'-phosphate as a co-factor and the chemistry underlying the functioning of MocR/GabR-type regulators typically requires a system-specific low molecular mass effector molecule. Through ligand binding studies with purified EnuR, we identified N-(alpha)-L-acetyl-2,4-diaminobutyric acid and L-2,4-diaminobutyric acid as inducers for EnuR that are generated through ectoine catabolism. AsnC/Lrp-type proteins can wrap DNA into nucleosome-like structures, and we found that the asnC gene was essential for use of ectoines as nutrients. Furthermore, we discovered through transposon mutagenesis that the NtrYX two-component system is required for their catabolism. Database searches suggest that our findings have important ramifications for an understanding of the molecular biology of most microbial consumers of ectoines.

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The aspartate aminotransferase-like domain of Firmicutes MocR transcriptional regulators

Cited by 16 publications

References 43 publications

The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

Negative Regulation of Ectoine Uptake and Catabolism in Sinorhizobium meliloti: Characterization of the EhuR Gene

Transcriptional regulation of ectoine catabolism in response to multiple metabolic and environmental cues

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