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Database: PROSITE(DOC)
Entry: PDOC00861
LinkDB: PDOC00861
Original site: PDOC00861 
{PDOC00861}
{PS01117; HTH_MARR_1}
{PS50995; HTH_MARR_2}
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* MarR-type HTH domain signature and profile *
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The  marR-type  HTH  domain  is  a DNA-binding, winged helix-turn-helix (wHTH)
domain  of  about  135  amino acids present in transcription regulators of the
marR/slyA  family,  involved in the development of antibiotic resistance. This
family  of  transcription  regulators  is named after Escherichia coli marR, a
repressor  of  genes  which  activate  the  multiple antibiotic resistance and
oxidative  stress  regulons, and after slyA from Salmonella typhimurium and E.
coli, a transcription regulator that is required for virulence and survival in
the  macrophage  environment.  Regulators  with  the  marR-type HTH domain are
present in bacteria and archaea and control a variety of biological functions,
including resistance to multiple antibiotics, household disinfectants, organic
solvents,  oxidative  stress  agents  and  regulation  of the virulence factor
synthesis  in pathogens of humans and plants. Many of the marR-like regulators
respond to aromatic compounds [1,2,3].

The  crystal structures of marR, mexR and slyA have been determined and show a
winged  HTH  DNA-binding core flanked by helices involved in dimerization (see
<PDB:1LJ9>). The DNA-binding domains are ascribed to the superfamily of winged
helix   proteins,   containing   a   three   (four)-helix  (H)  bundle  and  a
three-stranded     antiparallel    beta-sheet    (B)    in    the    topology:
H1-(H1')-H2-B1-H3-H4-B2-B3-H5-H6.    Helices    3    and    4   comprise   the
helix-turn-helix  motif  and  the  beta-sheet  is  called the wing. Helix 4 is
termed  the recognition helix, like in other HTHs where it binds the DNA major
groove. The helices 1, 5 and 6 are involved in dimerization, as most marR-like
transcription regulators form dimers [3,4,5].

Some proteins known to contain a marR-type HTH domain:

 - Escherichia  coli  marR,  a transcription repressor of chromosomal multiple
   antibiotic resistance (mar) in diverse bacteria [1,4].
 - Salmonella  typhimurium  and  E.  coli  slyA, a transcription activator for
   molecular chaperones, proteins involved in acid resistance and in virulence
   and a repressor for the expression of several biosynthetic enzymes.
 - Pseudomonas  aeruginosa  mexR,  a transcription repressor of the mexAB-oprM
   multidrug  efflux  operon,  a  major  determinant for broad resistance. The
   allosteric mechanism for the regulation of DNA binding seems to differ from
   that of marR [5].
 - Rhodopseudomonas   palustris   badR,  a  transcription  activator  for  the
   anaerobic degradation of benzoate [2].
 - Escherichia  coli mprA (emrR), a repressor of the multidrug resistance pump
   emrAB operon.
 - Erwinia  chrysanthemi  pecS,  a  transcription  regulator  for synthesis of
   pectinase, cellulase and other key factors for plant infection.
 - Bacillus subtilis hpr, a repressor of protease production and sporulation.
 - Butyrivibrio  fibrisolvens  cinR,  a  transcription  repressor of cinnamoyl
   ester hydrolase for ruminal degradation of plant material.

As  a  signature  pattern,  we have selected a 34 residue segment showing high
conservation  within this family. This conserved region from helix 3 to strand
3  is  located  in  the  DNA  binding domain. We also developed a profile that
covers  the  entire wHTH, including helix 1 and the conserved part of helix 6,
and which allows a more sensitive detection.

-Consensus pattern: [STNAQ]-[LIAMV]-x(0,1)-[RNGSYKE]-x(4,5)-[LM]-[EIVLA]-x(2)-
                    [GESD]-[LFYWHA]-[LIVC]-x(7)-[DNS]-[RKQG]-[RK]-x(6)-[TS]-
                    x(2)-[GAS]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Alekshun M.N., Levy S.B.
     "The mar regulon: multiple resistance to antibiotics and other toxic
     chemicals."
     Trends Microbiol. 7:410-413(1999).
     PubMed=10498949
[ 2] Egland P.G., Harwood C.S.
     "BadR, a new MarR family member, regulates anaerobic benzoate
     degradation by Rhodopseudomonas palustris in concert with AadR, an Fnr
     family member."
     J. Bacteriol. 181:2102-2109(1999).
     PubMed=10094687
[ 3] Wu R.Y., Zhang R.G., Zagnitko O., Dementieva I., Maltzev N.,
     Watson J.D., Laskowski R., Gornicki P., Joachimiak A.
     "Crystal structure of Enterococcus faecalis SlyA-like transcriptional
     factor."
     J. Biol. Chem. 278:20240-20244(2003).
     PubMed=12649270; DOI=10.1074/jbc.M300292200
[ 4] Alekshun M.N., Levy S.B., Mealy T.R., Seaton B.A., Head J.F.
     "The crystal structure of MarR, a regulator of multiple antibiotic
     resistance, at 2.3 A resolution."
     Nat. Struct. Biol. 8:710-714(2001).
     PubMed=11473263; DOI=10.1038/90429
[ 5] Lim D., Poole K., Strynadka N.C.J.
     "Crystal structure of the MexR repressor of the mexRAB-oprM multidrug
     efflux operon of Pseudomonas aeruginosa."
     J. Biol. Chem. 277:29253-29259(2002).
     PubMed=12034710; DOI=10.1074/jbc.M111381200
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