title: GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization.
abstract: BACKGROUND
  Mycobacterium smegmatis is fast growing non-pathogenic mycobacteria. This organism has been widely used as a model organism to study the biology of other virulent and extremely slow growing species like Mycobacterium tuberculosis. Based on the homology of the N-terminal DNA binding domain, the recently sequenced genome of M. smegmatis has been shown to possess several putative GntR regulators. A striking characteristic feature of this family of regulators is that they possess a conserved N-terminal DNA binding domain and a diverse C-terminal domain involved in the effector binding and/or oligomerization. Since the physiological role of these regulators is critically dependent upon effector binding and operator sites, we have analysed and classified these regulators into their specific subfamilies and identified their potential binding sites.
  
  
  RESULTS
  The sequence analysis of M. smegmatis putative GntRs has revealed that FadR, HutC, MocR and the YtrA-like regulators are encoded by 45, 8, 8 and 1 genes respectively. Further out of 45 FadR-like regulators, 19 were classified into the FadR group and 26 into the VanR group. All these proteins showed similar secondary structural elements specific to their respective subfamilies except MSMEG_3959, which showed additional secondary structural elements. Using the reciprocal BLAST searches, we further identified the orthologs of these regulators in Bacillus subtilis and other mycobacteria. Since the expression of many regulators is auto-regulatory, we have identified potential operator sites for a number of these GntR regulators by analyzing the upstream sequences.
  
  
  CONCLUSIONS
  This study helps in extending the annotation of M. smegmatis GntR proteins. It identifies the GntR regulators of M. smegmatis that could serve as a model for studying orthologous regulators from virulent as well as other saprophytic mycobacteria. This study also sheds some light on the nucleotide preferences in the target-motifs of GntRs thus providing important leads for initiating the experimental characterization of these proteins, construction of the gene regulatory network for these regulators and an understanding of the influence of these proteins on the physiology of the mycobacteria.
authors: Computational and Functional Genomics Group, Sun Centre of Excellence in Medical Bioinformatics, Centre for DNA Fingerprinting and Diagnostics, EMBnet India Node, Hyderabad 500076, India. vaibhav@cdfd.org.in
authors: Vaibhav
authors: V
authors: Vindal
authors: Katta
authors: K
authors: Suma
authors: Akash
authors: A
authors: Ranjan
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D020102:Mycobacterium smegmatis / Q000235:genetics*; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000145:classification / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C057119:FadR protein, Bacteria; D012097:Repressor Proteins; D014157:Transcription Factors
references: Microbiology. 2001 Apr;147(Pt 4):1069-77
references: 11283302
references: Res Microbiol. 2000 Dec;151(10):845-51
references: 11191810
references: J Biol Chem. 2002 Apr 12;277(15):12507-15
references: 11756427
references: FEMS Microbiol Lett. 2002 May 7;210(2):193-9
references: 12044674
references: Mol Microbiol. 2002 Jul;45(2):569-83
references: 12123465
references: FEMS Microbiol Lett. 2003 May 16;222(1):17-23
references: 12757941
references: J Bacteriol. 2003 Aug;185(15):4315-25
references: 12867439
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W318-20
references: 15215402
references: Nucleic Acids Res. 2004;32(11):3418-26
references: 15247334
references: Science. 1967 Jan 20;155(3760):279-84
references: 5334057
references: Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
references: 2849754
references: J Biol Chem. 1990 Mar 15;265(8):4461-71
references: 2155230
references: J Bacteriol. 1990 Sep;172(9):5470-6
references: 2203753
references: J Mol Biol. 1990 Oct 5;215(3):403-10
references: 2231712
references: J Biol Chem. 1991 Feb 5;266(4):2567-72
references: 1990006
references: FEMS Microbiol Lett. 1991 Apr 15;63(2-3):291-5
references: 2060763
references: Mol Microbiol. 1991 May;5(5):1081-9
references: 1659648
references: FEBS Lett. 1994 Dec 19;356(2-3):183-7
references: 7805834
references: Mol Microbiol. 1995 Feb;15(3):519-29
references: 7783622
references: Comput Appl Biosci. 1996 Aug;12(4):357-8
references: 8902363
references: J Biol Chem. 1999 Jan 15;274(3):1745-52
references: 9880556
references: Bioinformatics. 1998;14(9):755-63
references: 9918945
references: Bioinformatics. 1998;14(10):892-3
references: 9927721
references: J Bacteriol. 1999 Jun;181(11):3419-26
references: 10348853
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D192-6
references: 15608175
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W72-6
references: 15980571
references: J Bacteriol. 2006 Jan;188(2):441-9
references: 16385033
references: FEBS Lett. 2006 May 15;580(11):2567-76
references: 16631750
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W584-7
references: 16845075
references: BMC Bioinformatics. 2006;7:270
references: 16729895
references: Tuberculosis (Edinb). 2007 May;87(3):242-7
references: 17194626
references: BMC Bioinformatics. 2006;7 Suppl 5:S9
references: 17254314
references: J Mol Biol. 2000 Jun 2;299(2):499-520
references: 10860755
references: J Bacteriol. 2000 Oct;182(19):5454-61
references: 10986249
references: Eur J Biochem. 2000 Dec;267(24):7224-30
references: 11106435
references: Microbiology. 2001 Aug;147(Pt 8):2103-12
references: 11495988