Structural characterization of the involvement of SigC in the regulation of the gene expression of pathogenic Mycobacterium ulcerans.
Mycobacterium ulcerans is the causative agent of the Buruli ulcers in humans. This disease is a devastating necrotic disease of the subcutaneous tissue. Currently there are very few drugs to prevent the Buruli ulcers. This human pathogen is carried by aquatic insects. The gene sequence of this pathogenic organism has recently been identified. In the present study an attempt has been made to analyze the structural characteristics of the SigC protein from Mycobacterium ulcerans. Sequence analyses of SigC reveal that it belongs to the family of sigma factors, which are involved in DNA binding at promoter sites, and play a role in transcription initiation. Homology modeling was employed to construct the three-dimensional structure of the protein and the model was analyzed. SigC protein has a distinct helix-turn-helix DNA binding motif. It is compared to other members of the DNA binding proteins. The modeled structure of SigC has been used to dock on the promoter DNA to predict the favourable binding interactions of the protein, which are responsible for the gene expressions in the organism. These interactions have been used to predict the plausible mechanism of the process. Since this is the first structural work regarding the interactions of SigC protein and its promoter DNA, this study may contribute in the realm of structure based drug design approaches to produce drugs against this harmful organism to control its proliferation and spreading of Buruli ulcer.
Bagchi
Angshuman
A
Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. abagchi@iupui.edu
D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D019911:Mycobacterium ulcerans / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012808:Sigma Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C081467:sigC protein, Bacteria