title: Transcription regulation by steroid hormones: a computer simulation study.
abstract: Three-dimensional structures of complexes of 66 amino acid-DNA binding domains of human progesterone (hPR), estrogen (hER) and glucocorticoid (hGR) receptors (proteins), with ten base pair DNA duplexes: d(AGGTCATGCT).d(AGCATGACCT) and d(AGAACATGCT).d(AGCATGTTCT) were obtained using computer modeling and molecular mechanics techniques. Cartesian coordinates for the proteins were obtained from: 1) structural data of hER and hGR by NMR spectroscopy; 2) steric constraints imposed by tetrahedral coordination of the zinc ion to Cys residues, and 3) energy minimization in torsional and cartesian space. The proteins were made to interact with DNA (in B-form) in major groove through alpha-helical linker between the two zinc fingers. The geometry of the complexes was obtained by allowing them to slide, glide, penetrate in to and out of the groove, and to rotate about the helical axis. The complexes were energy minimized. Also maximized was the number of H-bonds between proteins and DNA. The complex structures were refined by molecular mechanics using AMBER 3.0. Structural parameters of DNA were analyzed in each complex and compared with those of native DNA optimized separately. The stereochemical differences of the complexes are discussed.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi.
authors.forename: V
authors.initials: V
authors.lastname: Kothekar
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006728:Hormones / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016415:Sequence Alignment; D013256:Steroids / Q000502:physiology*; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D006728:Hormones; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D013256:Steroids; D004247:DNA