title: Structural modeling and DNA binding autoinhibition analysis of Ergp55, a critical transcription factor in prostate cancer.
abstract: BACKGROUND
  The Ergp55 protein belongs to Ets family of transcription factor. The Ets proteins are highly conserved in their DNA binding domain and involved in various development processes and regulation of cancer metabolism. To study the structure and DNA binding autoinhibition mechanism of Ergp55 protein, we have produced full length and smaller polypeptides of Ergp55 protein in E. coli and characterized using various biophysical techniques.
  
  
  RESULTS
  The Ergp55 polypeptides contain large amount of α-helix and random coil structures as measured by circular dichorism spectroscopy. The full length Ergp55 forms a flexible and elongated molecule as revealed by molecular modeling, dynamics simulation and structural prediction algorithms. The binding analyses of Ergp55 polypeptides with target DNA sequences of E74 and cfos promoters indicate that longer fragments of Ergp55 (beyond the Ets domain) showed the evidence of auto-inhibition. This study also revealed the parts of Ergp55 protein that mediate auto-inhibition.
  
  
  CONCLUSIONS
  The current study will aid in designing the compounds that stabilize the inhibited form of Ergp55 and inhibit its binding to promoter DNA. It will contribute in the development of drugs targeting Ergp55 for the prostate cancer treatment.
authors: Structural Biology Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Shanti P
authors: SP
authors: Gangwar
authors: Sharmistha
authors: S
authors: Dey
authors: Ajay K
authors: AK
authors: Saxena
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008297:Male; D008961:Models, Structural; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D050784:Proto-Oncogene Protein c-ets-1 / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C577104:Ergp55 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D014157:Transcription Factors; D004247:DNA