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

Abstract

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.

Inhibition of glycine cleavage system by pyridoxine 5′‐phosphate causes synthetic lethality in glyA yggS and serA yggS in Escherichia coli

“…In addition to the coenzyme function, PLP may function as an antioxidant (Bilski et al , ) and modulator of steroid hormone (Tully et al , ) or P2X purinoceptor7 (Lambrecht et al , ; Thériault et al , ). Most of the bacteria utilize PLP‐dependent transcriptional factors to modulate metabolisms of vitamin B 6 and/or amino acid (Belitsky, , ; Takenaka et al , ; Tramonti et al , ).…”

Allosteric feedback inhibition of pyridoxine 5′-phosphate oxidase from Escherichia coli

“…Pyridoxal 5Ј-phosphate (PLP), 2 the catalytically active form of vitamin B 6 , is involved in many crucial metabolic pathways and plays a fundamental physiological role in all living organisms (1). PLP also performs biological functions other than catalysis, such as those of reactive oxygen species scavenger in plants (2,3) and Plasmodium falciparum (4), transcriptional regulator in Eubacteria (5), and virulence factor in Helicobacter pylori and Mycobacterium tuberculosis (6,7). Because of its aldehyde group, PLP is a very reactive molecule that readily combines with thiols and amines.…”

The ups and downs of ectoine: structural enzymology of a major microbial stress protectant and versatile nutrient

“…Their transcription is strongly up-regulated when ectoines are present in the growth medium (Jebbar et al 2005;Schulz et al 2017a;Yu et al 2017) but ectoines are not the true inducers (see below) (Schulz et al 2017a). Most inspected ectoine/5-hydroxyectoine catabolic gene clusters [456 out of 539 (Schulz et al 2017a);] contain a gene encoding a member (EhuR/EnuR) of the MocR/GabRfamily of transcriptional regulators (Tramonti et al 2018). Detailed studies on the EhuR/EnuR regulatory proteins from S. meliloti and R. pomeroyi identified the degradation intermediates N-α-ADABA and DABA as system-specific inducers and ligands for EhuR/EnuR (Schulz et al 2017a;Yu et al 2017).…”