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12  structures 1820  species 1  interaction 2149  sequences 19  architectures

Family: LexA_DNA_bind (PF01726)

Summary: LexA DNA binding domain

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This is the Wikipedia entry entitled "Repressor lexA". More...

Repressor lexA Edit Wikipedia article

LexA DNA binding domain
PDB 1jhh EBI.jpg
lexa s119a mutant
Identifiers
Symbol LexA_DNA_bind
Pfam PF01726
Pfam clan CL0123
InterPro IPR006199
SCOP 1leb
SUPERFAMILY 1leb

Repressor LexA or LexA is a transcriptional repressor (EC 3.4.21.88) that represses SOS response genes coding primarily for error-prone DNA polymerases, DNA repair enzymes and cell division inhibitors.[1] LexA forms de facto a two-component regulatory system with RecA, which senses DNA damage at stalled replication forks, forming monofilaments and acquiring an active conformation capable of binding to LexA and causing LexA to cleave itself, in a process called autoproteolysis.[2]

DNA damage can be inflicted by the action of antibiotics, bacteriophages and UV light.[1] Of potential clinical interest is the induction of the SOS response by antibiotics, such as ciprofloxacin. Bacteria require topoisomerases such as DNA gyrase or topoisomerase IV for DNA replication. Antibiotics such as ciprofloxacin are able to prevent the action of these molecules by attaching themselves to the gyrase - DNA complex, leading to replication fork stall and the induction of the SOS response. The expression of error-prone polymerases under the SOS response increases the basal mutation rate of bacteria. While mutations are often lethal to the cell, they can also enhance survival. In the specific case of topoisomerases, some bacteria have mutated one of their amino acids so that the ciproflaxin can only create a weak bond to the topoisomerase. This is one of the methods that bacteria use to become resistant to antibiotics. Ciprofloxacin treatment can therefore potentially lead to the generation of mutations that may render bacteria resistant to ciprofloxacin. In addition, ciprofloxacin has also been shown to induce via the SOS response dissemination of virulence factors [3] and antibiotic resistance determinants,[4] as well as the activation of integron integrases,[5] potentially increasing the likelihood of acquisition and dissemination of antibiotic resistance by bacteria.[1]

Impaired LexA proteolysis has been shown to interfere with ciprofloxacin resistance.[6] This offers potential for combination therapy that combines quinolones with strategies aimed at interfering with the action of LexA, either directly or via RecA.

LexA contains a DNA binding domain. The winged HTH motif of LexA is a variant form of the helix-turn-helix DNA binding motif.[7] it is usually located at the N-terminus of the protein.[2]

References

  1. ^ a b c Erill I, Campoy S, Barbe J (2007). "Aeons of distress: an evolutionary perspective on the bacterial SOS response". FEMS Microbiol Rev. 6: 637–656. doi:10.1111/j.1574-6976.2007.00082.x. PMID 17883408. 
  2. ^ a b Butala M, Zgur-Bertok D, Busby SJ (2009). "The bacterial LexA transcriptional repressor". Cell Mol Life Sci. 66: 82–93. doi:10.1007/s00018-008-8378-6. PMID 18726173. 
  3. ^ Ubeda C, Maiques E, Knecht E, Lasa I, Novick RP, Penadés JR (2005). "Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci". Mol Microbiol. 56 (3): 836–844. doi:10.1111/j.1365-2958.2005.04584.x. PMID 15819636. 
  4. ^ Beaber JW, Hochhut B, Waldor MK (2004). "SOS response promotes horizontal dissemination of antibiotic resistance genes". Nature 427 (6969): 72–74. doi:10.1038/nature02241. PMID 14688795. 
  5. ^ Guerin E, Cambray G, Sanchez-Alberola N, Campoy S, Erill I, Da Re S, Gonzalez-Zorn B, Barbé J, Ploy MC, Mazel D (2009). "The SOS response controls integron recombination". Science 324 (5930): 1034. doi:10.1126/science.1172914. PMID 19460999. 
  6. ^ Cirz RT, Chin JK, Andes DR, et al. (2005). "Inhibition of mutation and combating the evolution of antibiotic resistance". PLoS Biol. 3 (6): e176. doi:10.1371/journal.pbio.0030176. PMC 1088971. PMID 15869329. 
  7. ^ Fogh RH, Ottleben G, Ruterjans H, Schnarr M, Boelens R, Kaptein R (September 1994). "Solution structure of the LexA repressor DNA binding domain determined by 1H NMR spectroscopy". EMBO J. 13 (17): 3936–44. PMC 395313. PMID 8076591. 

This article incorporates text from the public domain Pfam and InterPro IPR006199

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

LexA DNA binding domain Provide feedback

This is the DNA binding domain of the LexA SOS regulon repressor which prevents expression of DNA repair proteins. The aligned region contains a variant form of the helix-turn-helix DNA binding motif [1]. This domain is found associated with PF00717 the auto-proteolytic domain of LexA EC:3.4.21.88.

Literature references

  1. Fogh RH, Ottleben G, Ruterjans H, Schnarr M, Boelens R, Kaptein R; , EMBO J 1994;13:3936-3944.: Solution structure of the LexA repressor DNA binding domain determined by 1H NMR spectroscopy. PUBMED:8076591 EPMC:8076591


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006199

The LexA SOS regulon repressor prevents the expression of DNA repair proteins in bacteria. This entry represents the DNA-binding domain, which contains a variant form of the helix-turn-helix DNA binding motif [PUBMED:8076591].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 254 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like Arg_repressor ARID B-block_TFIIIC Bac_DnaA_C BetR Bot1p BrkDBD Cdc6_C CENP-B_N Cro Crp CSN8_PSD8_EIF3K Cullin_Nedd8 CUT DDRGK DEP Dimerisation Dimerisation2 DsrD DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4447 DUF480 DUF739 DUF742 DUF977 E2F_TDP EAP30 ELL ESCRT-II Ets Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_C FokI_N Forkhead Ftsk_gamma FUR GcrA GerE GntR HARE-HTH HemN_C HNF-1_N Homeobox Homeobox_KN Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_5 HTH_6 HTH_7 HTH_8 HTH_9 HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MarR MarR_2 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 Mor MotA_activ MqsA_antitoxin MRP-L20 Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NUMOD1 OST-HTH P22_Cro PaaX PadR PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_rep_org_N Phage_terminase Pou Pox_D5 PuR_N Put_DNA-bind_N Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RP-C RPA RPA_C RQC Rrf2 RTP RuvB_C SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SLIDE SMC_ScpB SpoIIID STN1_2 Sulfolobus_pRN SWIRM TBPIP Terminase_5 TetR_N TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB Trp_repressor UPF0122 Vir_act_alpha_C YdaS_antitoxin YjcQ YokU z-alpha

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(9)
Full
(2149)
Representative proteomes UniProt
(9051)
NCBI
(10416)
Meta
(1668)
RP15
(637)
RP35
(1807)
RP55
(3038)
RP75
(4752)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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  Seed
(9)
Full
(2149)
Representative proteomes UniProt
(9051)
NCBI
(10416)
Meta
(1668)
RP15
(637)
RP35
(1807)
RP55
(3038)
RP75
(4752)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(9)
Full
(2149)
Representative proteomes UniProt
(9051)
NCBI
(10416)
Meta
(1668)
RP15
(637)
RP35
(1807)
RP55
(3038)
RP75
(4752)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1975 (release 4.1)
Previous IDs: none
Type: Domain
Author: Bashton M, Bateman A
Number in seed: 9
Number in full: 2149
Average length of the domain: 64.10 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 29.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.7 23.7
Trusted cut-off 23.7 23.7
Noise cut-off 23.6 23.6
Model length: 65
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There is 1 interaction for this family. More...

LexA_DNA_bind

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LexA_DNA_bind domain has been found. There are 12 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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