title: Optimizing the Photocontrol of bZIP Coiled Coils with Azobenzene Crosslinkers: Role of the Crosslinking Site.
abstract: DNA binding by bZIP-type coiled-coil proteins can be inhibited by dominant negative versions of the proteins in which the N-terminal basic region is replaced by an acidic extension. Photocontrol of bZIP function can be achieved by introducing intramolecular azobenzene-based crosslinkers into dominant negatives. We show that the largest degree of photocontrol is achieved when the crosslinker is introduced into the zipper region of the dominant negative between Cys residues placed at f sites in the heptad segment showing the highest intrinsic helical propensity. The overall affinity of the dominant negative can then be tuned by varying the length of the acidic extension.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada).|Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, 71515 Assiut (Egypt).
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Ali
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada).
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Forbes
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada). awoolley@chem.utoronto.ca.
authors.forename: G Andrew
authors.initials: GA
authors.lastname: Woolley
mesh_terms: D000595:Amino Acid Sequence; D001391:Azo Compounds / Q000737:chemistry*; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000737:chemistry / Q000235:genetics; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D008027:Light; D008969:Molecular Sequence Data; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001391:Azo Compounds; D050976:Basic-Leucine Zipper Transcription Factors; D003432:Cross-Linking Reagents; D050882:CREB-Binding Protein; C009850:azobenzene
keywords: CREB; azobenzene; coiled coils; helical propensity; photocontrol