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PurR DNA-binding transcriptional repressor

Synonyms: PurR, PurR-Guanine, PurR-hypoxanthine
Summary:
PurR dimer controls several genes involved in purine nucleotide biosynthesis and its own synthesis [11, 12, 22]. This regulator necessarily binds two products of purine metabolism, hypoxanthine and guanine, to induce the conformational change that allows PurR to bind DNA []. PurR belongs to the GalR/LacI family [2], and it shows 35%, 33%, and 26% identity with CytR, GalR, and LacI, respectively [5]. As with other members of this group, PurR shows a helix-turn-helix motif in the N-terminal domain for DNA binding [5] and a ligand-binding and dimerization motif in the C-terminal domain that shows similarity with ligand binding sites of periplasmic sugar-binding proteins [][2] The two domains are connected by a hinge sequence that is also important for DNA binding and that can be cleavage by proteases when the protein is not bound to DNA [].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
PurR Non-Functional   Apo nd nd
PurR-Guanine Functional Allosteric Holo nd nd
PurR-hypoxanthine Functional Allosteric Holo [APPHINH], [HIFS] [1], [2], [3], [4], [5]
Evolutionary Family: GalR/LacI
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: purR
  Genome position: 1737844-1738869
  Length: 1026 bp / 341 aa
Operon name: purR
TU(s) encoding the TF:
Transcription unit        Promoter
purR
purRp


Regulon       
Regulated gene(s) carA, carB, codA, codB, cvpA, gcvH, gcvP, gcvT, glnB, glyA, guaA, guaB, hflD, prs, purA, purB, purC, purD, purE, purF, purH, purK, purL, purM, purN, purR, purT, pyrC, pyrD, speA, speB, ubiX
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
purine biosynthesis (15)
nucleotide and nucleoside conversions (7)
pyrimidine biosynthesis (5)
amino acids (5)
formyl-THF biosynthesis (5)
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Regulated operon(s) carAB, codBA, cvpA-purF-ubiX, gcvTHP, glrR-glnB, glyA, guaBA, hflD-purB, lolB-ispE-prs, purA, purC, purEK, purHD, purL, purMN, purR, purT, pyrC, pyrD, speAB
First gene in the operon(s) carA, codB, cvpA, gcvT, glnB, glyA, guaB, hflD, prs, purA, purC, purE, purH, purL, purM, purR, purT, pyrC, pyrD, speA
Simple and complex regulons CRP,DnaA,Fis,PurR
CRP,FNR,GcvA,Lrp,PurR
FNR,PurR
Fis,IHF,PepA,PurR,RutR
Fis,PurR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[PurR,-](21)


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 (Confirmed, Strong, Weak) References
  PurR-hypoxanthine repressor carAp1 Sigma70 -128.5 -228.5 carA, carB
tcttcttgctGCGCAAGCGTTTTCCAgaacaggtta
 29415 29430 [AIBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [6], [7], [8]
  PurR-hypoxanthine repressor codBp Sigma70 -36.5 -74.5 codB, codA
atatttccccACGAAAACGATTGCTTtttatcttca
 354840 354855 [AIBSCS], [APIORCISFBSCS], [CV(GEA/ROMA)], [GEA] [6], [9], [10]
  PurR-hypoxanthine repressor cvpAp1 Sigma70 -28.5 -65.5 cvpA, purF, ubiX
aggaaatcccTACGCAAACGTTTTCTttttctgtta
 2430821 2430836 [APIORCISFBSCS], [BCE], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [5], [6], [11], [12], [13]
  PurR-hypoxanthine repressor gcvTp Sigma70 7.5 -98.5 gcvT, gcvH, gcvP
gttcaggcaaAAGAGAACGATTGCGTtggggaccgg
 3050758 3050773 [AIBSCS], [APIORCISFBSCS], [CV(GEA/ROMA)], [GEA] [6], [14]
  PurR-hypoxanthine repressor glnBp1 Sigma70 -42.5 -75.5 glnB
cacgagctggATGCAAACGATTTCAAggaatgaatt
 2687476 2687491 [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [15]
  PurR-hypoxanthine repressor glnBp2 Sigma70 20.5 -75.5 glnB
cacgagctggATGCAAACGATTTCAAggaatgaatt
 2687476 2687491 [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [15]
  PurR-hypoxanthine repressor glyAp Sigma70 -59.5 -126.5 glyA
cgtagcctgaAGGTAATCGTTTGCGTaaattccttt
 2685626 2685641 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [6], [16], [17], [18]
  PurR-hypoxanthine repressor guaBp Sigma70 -24.5 -61.5 guaB, guaA
aaaggggtagATGCAATCGGTTACGCtctgtataat
 2634124 2634139 [AIBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [6], [12]
  PurR-hypoxanthine repressor hflDp Sigma70 892.5 837.5 hflD, purB
tttgctgccgACGCAATCGGTTACCTtgatgcaatc
 1191787 1191802 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [3], [6]
  PurR-hypoxanthine repressor prsp Sigma70 -48.5 -350.5 prs
aggttatcgcAAGAAAACGTTTTCGCgaggttgatg
 1262218 1262233 [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [15]
  PurR-hypoxanthine repressor purAp Sigma70 -90.5 -113.5 purA
ctacatgttgAGGAAAACGATTGGCTgaacaaaaaa
 4404566 4404581 [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [4], [6]
  PurR-hypoxanthine repressor purAp Sigma70 9.5 -14.5 purA
atccatttttAAGCAAACGGTGATTTtgaaaaatgg
 4404665 4404680 [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [4], [6]
  PurR-hypoxanthine repressor purCp Sigma70 2.5 -161.5 purC
ctgatatgatACGCAAACGTGTGCGTctgcaggaaa
 2597772 2597787 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [6], [11]
  PurR-hypoxanthine repressor purEp Sigma70 -37.5 -79.5 purE, purK
tttcacagccACGCAACCGTTTTCCTtgctctcttt
 553172 553187 [AIBSCS], [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [6], [11], [12], [19]
  PurR-hypoxanthine repressor purHp Sigma70 -20.5 -115.5 purH, purD
cgcgagcgttGCGCAAACGTTTTCGTtacaatgcgg
 4207640 4207655 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(GEA/ROMA)], [GEA] [6], [11]
  PurR-hypoxanthine repressor purLp Sigma70 -38.5 -84.5 purL
ttttatttccACGCAAACGGTTTCGTcagcgcatca
 2695620 2695635 [AIBSCS], [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [6], [11], [12]
  PurR-hypoxanthine repressor purMp Sigma70 -27.5 -71.5 purM, purN
taaagcagtcTCGCAAACGTTTGCTTTccctgttaga
 2621118 2621134 [AIBSCS], [APIORCISFBSCS], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [6], [12], [20], [21]
  PurR-hypoxanthine repressor purRp Sigma70 103.5 -52.5 purR
aggtgtgtaaAGGCAAACGTTTACCTtgcgattttg
 1737784 1737799 [APIORCISFBSCS], [BCE], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [6], [12], [22]
  PurR-hypoxanthine repressor purRp Sigma70 191.5 36.5 purR
gtagcgaaacGAGCAAACGTTTCCACtacaactgtg
 1737872 1737887 [APIORCISFBSCS], [BCE], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [12], [22]
  PurR-hypoxanthine repressor purTp Sigma70 -21.5 -45.5 purT
ataaagacacACGCAAACGTTTTCGTTtatactgcgc
 1930828 1930844 [AIBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [23]
  PurR-hypoxanthine repressor pyrCp Sigma70 -23.5 -59.5 pyrC
tttcgtgcaaAGGAAAACGTTTCCGCttatcctttg
 1122659 1122674 [APIORCISFBSCS], [BPP], [CV(CHIP-SV/GEA/ROMA)], [CV(CHIP-SV/SM)], [CV(GEA/ROMA)], [CV(GEA/ROMA/SM)], [GEA], [SM] [1], [24], [25]
  PurR-hypoxanthine repressor pyrDp Sigma70 -58.5 -94.5 pyrD
gaaacaggttCGGAAAACGTTTGCGTtttttttgcc
 1004666 1004681 [AIBSCS], [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [6], [25]
  PurR-hypoxanthine repressor speAp Sigma70 11.5 -126.5 speA, speB
tgttatgaaaAAGAAACCGGTTGCGCagttggagcg
 3086030 3086045 [APIORCISFBSCS], [BCE], [CV(GEA/ROMA)], [GEA] [15]


Alignment and PSSM for PurR TFBSs    

Aligned TFBS of PurR   
  Sequence
  ACGCAAACGTTTTCGTT
  ACGCAAACGTTTTCTTT
  GCGCAAACGTTTTCGTT
  ACGCAACCGTTTTCCTT
  ACGCAAACGGTTTCGTC
  ACGCAATCGGTTACCTT
  ACGCAAACGATTACCTT
  AGGCAAACGTTTACCTT
  GCGCAACCGGTTTCTTT
  GCGGAAACGTTTTCCTT
  AAGCAATCGTTTTCGTG
  ACGCAATCGTTCTCTTT
  TCGCAAACGTTTGCTTT
  ACGCAAACGTTTTCCGA
  GCGAAAACGTTTTCTTG
  ACGCAAACGTGTGCGTC
  GCGCAAGCGTTTTCCAG
  AGCCAATCGTTTTCCTC
  ATGCAATCGGTTACGCT
  GAGCAAACGTTTCCACT
  ATGCAAACGATTTCAAG
  AAGCAAACGGTGATTTT

Position weight matrix (PWM). PurR matrix-quality result    
A	15	3	0	1	22	22	14	0	0	2	0	0	5	0	2	2	1
C	0	15	1	20	0	0	2	22	0	0	0	1	1	21	8	2	3
G	6	2	21	1	0	0	1	0	22	5	1	1	2	0	6	1	4
T	1	2	0	0	0	0	5	0	0	15	21	20	14	1	6	17	14

Consensus    
;	consensus.strict             	aCGCAAaCGtTTtCctt
;	consensus.strict.rc          	AAGGAAAACGTTTGCGT
;	consensus.IUPAC              	rCGCAAaCGkTTtCstt
;	consensus.IUPAC.rc           	AASGAAAMCGTTTGCGY
;	consensus.regexp             	[ag]CGCAAaCG[gt]TTtC[cg]tt
;	consensus.regexp.rc          	AA[CG]GAAA[AC]CGTTTGCG[CT]

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    

 [APPHINH] Assay of protein purified to homogeneity from its native host

 [HIFS] Human inference of function from sequence

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [CV(CHIP-SV/GEA/ROMA)] cross validation(CHIP-SV/GEA/ROMA)

 [CV(GEA/ROMA)] cross validation(GEA/ROMA)

 [GEA] Gene expression analysis

 [APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [BCE] Binding of cellular extracts

 [CV(CHIP-SV/SM)] cross validation(CHIP-SV/SM)

 [CV(GEA/ROMA/SM)] cross validation(GEA/ROMA/SM)

 [SM] Site mutation


Reference(s)    

 [1] Choi KY., Zalkin H., 1990, Regulation of Escherichia coli pyrC by the purine regulon repressor protein., J Bacteriol 172(6):3201-7

 [2] Fukami-Kobayashi K., Tateno Y., Nishikawa K., 2003, Parallel evolution of ligand specificity between LacI/GalR family repressors and periplasmic sugar-binding proteins., Mol Biol Evol 20(2):267-77

 [3] He B., Smith JM., Zalkin H., 1992, Escherichia coli purB gene: cloning, nucleotide sequence, and regulation by purR., J Bacteriol 174(1):130-6

 [4] He B., Zalkin H., 1994, Regulation of Escherichia coli purA by purine repressor, one component of a dual control mechanism., J Bacteriol 176(4):1009-13

 [5] Rolfes RJ., Zalkin H., 1988, Escherichia coli gene purR encoding a repressor protein for purine nucleotide synthesis. Cloning, nucleotide sequence, and interaction with the purF operator., J Biol Chem 263(36):19653-61

 [6] Cho BK., Federowicz SA., Embree M., Park YS., Kim D., Palsson BO., 2011, The PurR regulon in Escherichia coli K-12 MG1655., Nucleic Acids Res 39(15):6456-64

 [7] Devroede N., Huysveld N., Charlier D., 2006, Mutational analysis of intervening sequences connecting the binding sites for integration host factor, PepA, PurR, and RNA polymerase in the control region of the Escherichia coli carAB operon, encoding carbamoylphosphate synthase., J Bacteriol 188(9):3236-45

 [8] Devroede N., Thia-Toong TL., Gigot D., Maes D., Charlier D., 2004, Purine and pyrimidine-specific repression of the Escherichia coli carAB operon are functionally and structurally coupled., J Mol Biol 336(1):25-42

 [9] Danielsen S., Kilstrup M., Barilla K., Jochimsen B., Neuhard J., 1992, Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase., Mol Microbiol 6(10):1335-44

 [10] Kilstrup M., Meng LM., Neuhard J., Nygaard P., 1989, Genetic evidence for a repressor of synthesis of cytosine deaminase and purine biosynthesis enzymes in Escherichia coli., J Bacteriol 171(4):2124-7

 [11] He B., Shiau A., Choi KY., Zalkin H., Smith JM., 1990, Genes of the Escherichia coli pur regulon are negatively controlled by a repressor-operator interaction., J Bacteriol 172(8):4555-62

 [12] Meng LM., Kilstrup M., Nygaard P., 1990, Autoregulation of PurR repressor synthesis and involvement of purR in the regulation of purB, purC, purL, purMN and guaBA expression in Escherichia coli., Eur J Biochem 187(2):373-9

 [13] Rolfes RJ., Zalkin H., 1988, Regulation of Escherichia coli purF. Mutations that define the promoter, operator, and purine repressor gene., J Biol Chem 263(36):19649-52

 [14] Wilson RL., Urbanowski ML., Stauffer GV., 1995, DNA binding sites of the LysR-type regulator GcvA in the gcv and gcvA control regions of Escherichia coli., J Bacteriol 177(17):4940-6

 [15] He B., Choi KY., Zalkin H., 1993, Regulation of Escherichia coli glnB, prsA, and speA by the purine repressor., J Bacteriol 175(11):3598-606

 [16] Lorenz E., Stauffer GV., 1995, Characterization of the MetR binding sites for the glyA gene of Escherichia coli., J Bacteriol 177(14):4113-20

 [17] Lorenz E., Stauffer GV., 1996, RNA polymerase, PurR and MetR interactions at the glyA promoter of Escherichia coli., Microbiology 142 ( Pt 7):1819-24

 [18] Steiert JG., Kubu C., Stauffer GV., 1992, The PurR binding site in the glyA promoter region of Escherichia coli., FEMS Microbiol Lett 78(2-3):299-304

 [19] Watanabe W., Sampei G., Aiba A., Mizobuchi K., 1989, Identification and sequence analysis of Escherichia coli purE and purK genes encoding 5'-phosphoribosyl-5-amino-4-imidazole carboxylase for de novo purine biosynthesis., J Bacteriol 171(1):198-204

 [20] Liu IF., Aedo S., Tse-Dinh YC., 2011, Resistance to topoisomerase cleavage complex induced lethality in Escherichia coli via titration of transcription regulators PurR and FNR., BMC Microbiol 11:261

 [21] Smith JM., Daum HA., 1986, Nucleotide sequence of the purM gene encoding 5'-phosphoribosyl-5-aminoimidazole synthetase of Escherichia coli K12., J Biol Chem 261(23):10632-6

 [22] Rolfes RJ., Zalkin H., 1990, Autoregulation of Escherichia coli purR requires two control sites downstream of the promoter., J Bacteriol 172(10):5758-66

 [23] Belliveau NM., Barnes SL., Ireland WT., Jones DL., Sweredoski MJ., Moradian A., Hess S., Kinney JB., Phillips R., 2018, Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria., Proc Natl Acad Sci U S A 115(21):E4796-E4805

 [24] Wilson HR., Chan PT., Turnbough CL., 1987, Nucleotide sequence and expression of the pyrC gene of Escherichia coli K-12., J Bacteriol 169(7):3051-8

 [25] Wilson HR., Turnbough CL., 1990, Role of the purine repressor in the regulation of pyrimidine gene expression in Escherichia coli K-12., J Bacteriol 172(6):3208-13


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