{PDOC00861}
{PS01117; HTH_MARR_1}
{PS50995; HTH_MARR_2}
{BEGIN}
**********************************************
* MarR-type HTH domain signature and profile *
**********************************************
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
{END}