title: De novo design of protein mimics of B-DNA.
abstract: Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr - the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B-DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem.
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Avenue, Medford, MA 02155, USA. krishna.kumar@tufts.edu.
authors.forename: Deniz
authors.initials: D
authors.lastname: Yüksel
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA. pbianco@buffalo.edu.
authors.forename: Piero R
authors.initials: PR
authors.lastname: Bianco
authors.affiliation: Department of Chemistry, Tufts University, 62 Talbot Avenue, Medford, MA 02155, USA. krishna.kumar@tufts.edu and Cancer Center, Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D059371:DNA, B-Form / Q000737:chemistry* / Q000378:metabolism; D015253:Deoxyribonucleases, Type I Site-Specific / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D059371:DNA, B-Form; D010455:Peptides; D011506:Proteins; D015253:Deoxyribonucleases, Type I Site-Specific