Structural modeling and DNA binding autoinhibition analysis of Ergp55, a critical transcription factor in prostate cancer

Shanti Gangwar, Sharmistha Dey, Ajay K. Saxena

Research output: Contribution to journalArticle

3 Citations (Scopus)

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. Significance: 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.

Original languageEnglish (US)
Article numbere39850
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 28 2012
Externally publishedYes

Fingerprint

prostatic neoplasms
Prostatic Neoplasms
Transcription Factors
transcription factors
DNA
polypeptides
Peptides
Proteins
proteins
automobiles
Proto-Oncogene Proteins c-ets
promoter regions
Escherichia coli Proteins
Molecular Dynamics Simulation
Drug Delivery Systems
Molecular modeling
Oncology
DNA-binding domains
DNA sequences
Spectrum Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Structural modeling and DNA binding autoinhibition analysis of Ergp55, a critical transcription factor in prostate cancer. / Gangwar, Shanti; Dey, Sharmistha; Saxena, Ajay K.

In: PLoS One, Vol. 7, No. 6, e39850, 28.06.2012.

Research output: Contribution to journalArticle

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