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NrdR DNA-binding transcriptional repressor

Synonyms: NrdR-Zn2+, NrdR-dATP, NrdR-ATP
Summary:
NrdR is a zinc-finger/ATP cone transcriptional regulatory protein that regulates the expression of several operons that encode ribonucleotide reductases (RNRs), according to the abundance of deoxyribonucleoside triphosphates (dNTPs) generated from ribonucleotides [2]. NrdR has an N-terminal zinc-finger-like DNA-binding domain and a C-terminal ATP cone domain. The ATP cone domain is similar to the allosteric domain found in some RNRs [1] NrdR is bound by approximately equal amounts of ATP and dATP in vivo [2] Triphosphates bind preferentially to NrdR compared to nucleoside monophosphates and triphosphates [2] NrdR is directly regulated by ATP, rather than ATP serving as the cofactor to facilitate dATP binding [2] The apo and holo forms of NrdR are capable of binding to DNA; furthermore, this binding capability is enhanced by high concentrations of zinc [] In Streptomyces coelicolor, it was shown that NrdR is an oligomeric protein that binds zinc, ATP, dATP, and the previously hypothesized NrdR box [].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NrdR-ATP Functional Allosteric Holo [AIFS] [1]
NrdR-Zn2+ Functional Allosteric Holo [AIFS], [APPHINH], [BPP], [HIFS], [IMP] [1]
NrdR-dATP Functional Allosteric Holo [AIFS] [1]
Evolutionary Family: NrdR
Connectivity class: Local Regulator
Gene name: nrdR
  Genome position: 433002-433451
  Length: 450 bp / 149 aa
Operon name: nrdR-ribDE-nusB-thiL-pgpA
TU(s) encoding the TF:
Transcription unit        Promoter
nrdR-ribDE-nusB-thiL-pgpA
nrdRp


Regulon       
Regulated gene(s) nrdA, nrdB, nrdD, nrdE, nrdF, nrdG, nrdH, nrdI, yfaE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
nucleotide and nucleoside conversions (4)
posttranslational modification (3)
2'-deoxyribonucleotide metabolism (1)
inhibition / activation of enzymes (1)
thioredoxin, glutaredoxin (1)
Regulated operon(s) nrdAB-yfaE, nrdDG, nrdHIEF
First gene in the operon(s) nrdA, nrdD, nrdH
Simple and complex regulons ArgP,CRP,DnaA,Fis,H-NS,NrdR
FNR,H-NS,NrdR
Fur,IscR,NrdR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NrdR,-](3)


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
  NrdR-Zn2+ repressor nrdAp Sigma70 -7.5 -117.5 nrdA, nrdB, yfaE
agggtcatttTCACACTATCTTGCAGtgaatcccaa
2344740 2344755 [BPP], [GEA], [HIBSCS], [SM] [1]
  NrdR-Zn2+ repressor nrdAp Sigma70 25.5 -85.5 nrdA, nrdB, yfaE
ccaaacatacCCCCTATATATAGTGTtctaagcagc
2344772 2344787 [BPP], [GEA], [HIBSCS], [SM] [1]
  NrdR-Zn2+ repressor nrdDp Sigma70 -22.5 -200.5 nrdD, nrdG
cgcattttaaAGTCTATATATAGTGCtttgcatcaa
4462853 4462868 [BPP], [GEA], [HIBSCS] [1]
  NrdR-Zn2+ repressor nrdDp Sigma70 9.5 -169.5 nrdD, nrdG
tagtcgattaATACAACATATTGGGTtgggacgcat
4462822 4462837 [BPP], [GEA], [HIBSCS] [1]
  NrdR-Zn2+ repressor nrdHp Sigma70 -45.5 -112.5 nrdH, nrdI, nrdE, nrdF
cgaccactatTTGCTATATATTGTGTggttgaatct
2800603 2800618 [BPP], [GEA], [HIBSCS] [1]
  NrdR-Zn2+ repressor nrdHp Sigma70 -14.5 -81.5 nrdH, nrdI, nrdE, nrdF
aatcttttttCAACTACATCTAGTATctctgtatca
2800634 2800649 [BPP], [GEA], [HIBSCS] [1]


Alignment and PSSM for NrdR TFBSs    

Position weight matrix (PWM).   
A	1	4	0	3	5	0	6	0	3	0	4	0	1	4	1
C	5	2	6	0	1	1	0	0	2	0	0	0	2	1	0
G	0	0	0	0	0	0	0	0	1	0	0	6	0	1	1
T	0	0	0	3	0	5	0	6	0	6	2	0	3	0	4

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    

 [AIFS] Automated inference of function from sequence

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

 [BPP] Binding of purified proteins

 [HIFS] Human inference of function from sequence

 [IMP] Inferred from mutant phenotype

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation



Reference(s)    

 [1] Torrents E., Grinberg I., Gorovitz-Harris B., Lundstrom H., Borovok I., Aharonowitz Y., Sjoberg BM., Cohen G., 2007, NrdR controls differential expression of the Escherichia coli ribonucleotide reductase genes., J Bacteriol 189(14):5012-21

 [2] McKethan BL., Spiro S., 2013, Cooperative and allosterically controlled nucleotide binding regulates the DNA binding activity of NrdR., Mol Microbiol 90(2):278-89



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