title: Homology modeling and virtual screening of ubiquitin conjugation enzyme E2A for designing a novel selective antagonist against cancer.
abstract: Cancer is a major health problem in the world. The initiation and progression of cancer is due to imbalance between the programmed cell growth and death. These processes are triggered by the ubiquitin family enzymes. The ubiquitin-like proteins are responsible for the cell metabolism. Ubiquitin-dependent proteolysis by the 26s proteasome plays a crucial role in cell cycle progression as well as in tumorigenesis. In the ubiquitin proteasomal degradation pathway, ubiquitin conjugation enzyme E2A (UBE2A) binds with ubiquitin ligase RAD18, results in polyubiquitation reaction and cell cycle progression. UBE2A is an important contributing factor for the control of tumorigenesis. In the present work, the 3D model of the protein UBE2A was generated by homology modeling technique. The generated 3D structure of the UBE2A was validated, and active site was identified using standard computational protocols. The active site was subjected to structure-based virtual screening using small molecule data banks, and new molecules were identified. The ADME properties of the new ligand molecules were predicted, and the new ligands are identified as potent UBE2A antagonists for cancer therapy.
authors.affiliation: a Department of Chemistry , University College of Science and.
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Ramatenki
authors.affiliation: b Department of Chemistry , Nizam College, Osmania University , Hyderabad , Telangana , India.
authors.forename: Sarita Rajender
authors.initials: SR
authors.lastname: Potlapally
authors.affiliation: a Department of Chemistry , University College of Science and.
authors.forename: Rama Krishna
authors.initials: RK
authors.lastname: Dumpati
authors.affiliation: a Department of Chemistry , University College of Science and.
authors.forename: Rajender
authors.initials: R
authors.lastname: Vadija
authors.affiliation: a Department of Chemistry , University College of Science and.
authors.forename: Uma
authors.initials: U
authors.lastname: Vuruputuri
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy*; D017386:Sequence Homology, Amino Acid; D054852:Small Molecule Libraries / Q000494:pharmacology*; D040681:Structural Homology, Protein; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D054852:Small Molecule Libraries; D025801:Ubiquitin; C471545:UBE2A protein, human; D044763:Ubiquitin-Conjugating Enzymes
keywords: ADME; RAD18; cancer therapy; tumorigenesis; ubiquitin ligase