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PdhR DNA-binding transcriptional dual regulator

Synonyms: PdhR-pyruvate, PdhR
Summary:
PdhR, "pyruvate dehydrogenase complex regulator," regulates genes involved in the pyruvate dehydrogenase complex [2, 3, 9, 10] Moreover, PdhR participates in positive regulation of fatty acid degradation genes and negative regulation of cell mobility genes. Gas chromatography analysis indicated an increase in free fatty acids in a mutant lacking PdhR [3] Activity of PdhR is controlled by pyruvate. In the absence of this compound, the PdhR regulator binds to its target promoters [3] This binding is antagonized by pyruvate [1, 2, 3] PdhR activates a set of genes for fatty acid degradation only in the absence of effector pyruvate. Therefore, the activation of the fatty acid degradation genes by PdhR could be lost in the presence of pyruvate. Likewise, RpoF-regulated synthesis of flagellar components is also controlled by the pyruvate-sensing PdhR. In the absence of PdhR, the expression level of the flagellar component increased, indicating a new model in which the level of flagella is controlled by the level of pyruvate [3] PdhR controls the synthesis of two key enzymes (Ndh and CyoA) in the terminal electron transport system [1] the enzymes for producing pyruvate and the enzymes involved in the utilization of pyruvate as a substrate [3] The pdhR deletion mutant enhanced glucose metabolism under oxygen-limited conditions.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
PdhR Functional   Apo [EXP-IDA], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [2]
PdhR-pyruvate Non-Functional Allosteric Holo [EXP-IDA], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [2]
Evolutionary Family: GntR
TFBs length: 17
TFBs symmetry: inverted-repeat
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: pdhR
  Genome position: 122092-122856
  Length: 765 bp / 254 aa
Operon name: pdhR-aceEF-lpd
TU(s) encoding the TF:
Transcription unit        Promoter
pdhR-aceEF-lpdA
pdhRp
pdhR-aceEF-lpdA
pdhRp2


Regulon       
Regulated gene(s) aceE, aceF, cyoA, cyoB, cyoC, cyoD, cyoE, ddlB, fecA, fecB, fecC, fecD, fecE, ftsA, ftsI, ftsL, ftsQ, ftsW, ftsZ, glcA, glcB, glcD, glcE, glcF, glcG, grcA, hemL, hha, lpd, lpxC, mraY, mraZ, murC, murD, murE, murF, murG, ndh, pdhR, rsmH, tomB
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (12)
murein (peptidoglycan) (8)
murein (8)
cell division (7)
aerobic respiration (6)
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Regulated operon(s) cyoABCDE, fecABCDE, glcDEFGBA, grcA, hemL, mraZ-rsmH-ftsLI-murEF-mraY-murD-ftsW-murGC-ddlB-ftsQAZ-lpxC, ndh, pdhR-aceEF-lpd, tomB-hha
First gene in the operon(s) cyoA, fecA, glcD, grcA, hemL, mraZ, ndh, pdhR, tomB
Simple and complex regulons ArcA,CRP,Cra,CusR,FNR,Fis,Fur,GadE,HprR,PdhR
ArcA,CRP,FNR,Fis,Fur,PdhR
ArcA,FNR,Fis,Fur,IHF,NsrR,PdhR
ArcA,GlcC,IHF,PdhR
BasR,CpxR,PdhR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[PdhR,+](1)
[PdhR,-](9)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  PdhR repressor cyoAp Sigma70 -177.0 -220.0 cyoA, cyoB, cyoC, cyoD, cyoE
ttttatttcaCATTGGTTATACCAATTgcccgcccag
 451822 451838 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [4]
  PdhR activator fecAp nd -21.0 -71.0 fecA, fecB, fecC, fecD, fecE
taaggaaaatAATTCTTATTTCGATTGtcctttttac
 4516740 4516756 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS] W [5], [5]
  PdhR repressor glcDp Sigma70 -56.0 -111.0 glcD, glcE, glcF, glcG, glcB, glcA
gctggaaaaaAAATGGTCTGACCGGTAgctaaagaga
 3128124 3128140 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [4], [6], [6]
  PdhR repressor grcAp1 Sigma70 17.0 -58.0 grcA
actcaagcaaCAATGGTTTTACCAATTggccgcgaca
 2716499 2716515 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ] S [4], [7], [7]
  PdhR repressor hemLp Sigma28 -165.0 -204.0 hemL
aatgatcactTATTGGTCATACAAATAagatgacggc
 175078 175094 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [1], [1]
  PdhR repressor mraZp Sigma70 -42.0 -80.0 mraZ, rsmH, ftsL, ftsI, murE, murF, mraY, murD, ftsW, murG, murC, ddlB, ftsQ, ftsA, ftsZ, lpxC
tatgccttgtGACTGGCTTGACAAGCTtttcctcagc
 89546 89562 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [6], [6]
  PdhR repressor ndhp Sigma70 -35.0 -128.0 ndh
ttaacatcaaTTTTGGTATGACCAATGcaccattcat
 1165949 1165965 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [3], [3], [4]
  PdhR repressor pdhRp Sigma70 19.0 -40.0 pdhR, aceE, aceF, lpd
acagacatgaAATTGGTAAGACCAATTgacttcggca
 122044 122060 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [2], [3], [3], [4], [6], [6], [8], [8]
  PdhR repressor pdhRp2 Sigma38 19.0 -40.0 pdhR, aceE, aceF, lpd
acagacatgaAATTGGTAAGACCAATTgacttcggca
 122044 122060 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-GSELEX], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [2], [3], [3], [4], [6], [6], [8], [8]
  PdhR repressor tomBp Sigma70 -178.0 -264.0 tomB, hha
gcaatcctggTATTAGTGTCACCAATTtcatctggcg
 480964 480980 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [1], [1]



High-throughput Transcription factor binding sites (TFBSs)
      

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Center Position Growth Condition Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  PdhR activator ppsR Gene nd
attcatgccgAGTTGGTTATACCAAAGcaccagcggt
1787066 1787082 1787074.0 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [3]
  PdhR activator ppsA Gene nd
attcatgccgAGTTGGTTATACCAAAGcaccagcggt
1787066 1787082 1787074.0 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [3]
Other High-throughput regulatory interactions with weak evidence


Alignment and PSSM for PdhR TFBSs    

Aligned TFBS of PdhR   
  Sequence
  CAATTGGTCTTACCAATTT
  CAATTGGTATAACCAATGT
  CAATTGGTAAAACCATTGT
  CTACCGGTCAGACCATTTT
  GCATTGGTCATACCAAAAT
  TTATTGGTCATACAAATAA
  GTATTAGTGTCACCAATTT
  CAATCGAAATAAGAATTAT
  TGACTGGCTTGACAAGCTT

Position weight matrix (PWM). PdhR matrix-quality result    
A	0	4	9	0	0	1	1	1	3	4	3	9	0	3	9	5	1	3	1
C	5	1	0	2	2	0	0	1	4	0	1	0	8	6	0	0	1	0	0
G	2	1	0	0	0	8	8	0	1	0	2	0	1	0	0	1	0	2	0
T	2	3	0	7	7	0	0	7	1	5	3	0	0	0	0	3	7	4	8

Consensus    
;	consensus.strict             	caAttGGtctaACCAattT
;	consensus.strict.rc          	AAATTGGTTAGACCAATTG
;	consensus.IUPAC              	swAyyGGtmwdACMAwtdT
;	consensus.IUPAC.rc           	AHAWTKGTHWKACCRRTWS
;	consensus.regexp             	[cg][at]A[ct][ct]GGt[ac][at][agt]AC[AC]A[at]t[agt]T
;	consensus.regexp.rc          	A[ACT]A[AT]T[GT]GT[ACT][AT][GT]ACC[AG][AG]T[AT][CG]

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


Evidence    

 [EXP-IDA] Inferred from direct assay

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [EXP-GSELEX] high throughput Genomic SELEX-chip evidence

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences

 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] Binding of cellular extracts


Reference(s)    

 [1] Ogasawara H., Ishida Y., Yamada K., Yamamoto K., Ishihama A., 2007, PdhR (pyruvate dehydrogenase complex regulator) controls the respiratory electron transport system in Escherichia coli., J Bacteriol 189(15):5534-41

 [2] Quail MA., Guest JR., 1995, Purification, characterization and mode of action of PdhR, the transcriptional repressor of the pdhR-aceEF-lpd operon of Escherichia coli., Mol Microbiol 15(3):519-29

 [3] Anzai T., Imamura S., Ishihama A., Shimada T., 2020, Expanded roles of pyruvate-sensing PdhR in transcription regulation of the Escherichia coli K-12 genome: fatty acid catabolism and cell motility., Microb Genom 6(10)

 [4] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [5] Faith JJ., Hayete B., Thaden JT., Mogno I., Wierzbowski J., Cottarel G., Kasif S., Collins JJ., Gardner TS., 2007, Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles., PLoS Biol 5(1):e8

 [6] Gohler AK., Kokpinar O., Schmidt-Heck W., Geffers R., Guthke R., Rinas U., Schuster S., Jahreis K., Kaleta C., 2011, More than just a metabolic regulator - elucidation and validation of new targets of PdhR in Escherichia coli., BMC Syst Biol 5(1):197

 [7] Wyborn NR., Messenger SL., Henderson RA., Sawers G., Roberts RE., Attwood MM., Green J., 2002, Expression of the Escherichia coli yfiD gene responds to intracellular pH and reduces the accumulation of acidic metabolic end products., Microbiology 148(Pt 4):1015-26

 [8] Quail MA., Haydon DJ., Guest JR., 1994, The pdhR-aceEF-lpd operon of Escherichia coli expresses the pyruvate dehydrogenase complex., Mol Microbiol 12(1):95-104

 [9] Haydon DJ., Quail MA., Guest JR., 1993, A mutation causing constitutive synthesis of the pyruvate dehydrogenase complex in Escherichia coli is located within the pdhR gene., FEBS Lett 336(1):43-7

 [10] Urbanowski ML., Stauffer LT., Stauffer GV., 2000, The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli., Mol Microbiol 37(4):856-68

 [11] Maeda S, Shimizu K, Kihira C, Iwabu Y, Kato R, Sugimoto M, Fukiya S, Wada M, Yokota A, 2017, Pyruvate dehydrogenase complex regulator (PdhR) gene deletion boosts glucose metabolism in Escherichia coli under oxygen-limited culture conditions., J Biosci Bioeng, 123(4):437 10.1016/j.jbiosc.2016.11.004

 [12] Haydon DJ., Guest JR., 1991, A new family of bacterial regulatory proteins., FEMS Microbiol Lett 63(2-3):291-5

 [13] Dong JM., Taylor JS., Latour DJ., Iuchi S., Lin EC., 1993, Three overlapping lct genes involved in L-lactate utilization by Escherichia coli., J Bacteriol 175(20):6671-8

 [14] Buck D., Guest JR., 1989, Overexpression and site-directed mutagenesis of the succinyl-CoA synthetase of Escherichia coli and nucleotide sequence of a gene (g30) that is adjacent to the suc operon., Biochem J 260(3):737-47

 [15] Shimada T, Nakazawa K, Tachikawa T, Saito N, Niwa T, Taguchi H, Tanaka K, 2021, Acetate overflow metabolism regulates a major metabolic shift after glucose depletion in Escherichia coli., FEBS Lett, 595(15):2047 10.1002/1873-3468.14151


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