Amsacrine is an anilinoacridine derivative anticancer drug, used to treat a wide variety of malignancies. In cells, amsacrine poisons topoisomerase 2 by stabilizing DNA-drug-enzyme ternary complex. Presence of amsacrine increases the steady-state concentration of these ternary complexes which in turn hampers DNA replication and results in subsequent cell death. Due to reversible binding and rap...

Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading polyintercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator c...

Many proteins select special DNA sequences to form functional complexes. In one possible mechanism, protein molecules would scan DNA sequences by tracking a groove without complete dissociation. Upon dragging single molecules of DNA over a surface carrying fixed Escherichia coli RNA polymerase holoenzyme, we detected rotation of individual DNA molecules, providing direct evidence that a DNA-bin...

DNA shape variation and the associated variation in minor groove electrostatic potential are widely exploited by proteins for DNA recognition. Here we show that the hydroxyl radical cleavage pattern is a quantitative measure of DNA backbone solvent accessibility, minor groove width, and minor groove electrostatic potential, at single nucleotide resolution. We introduce maps of DNA shape and ele...

A crystal structure for a member of the AraC prokaryotic transcriptional activator family, MarA, in complex with its cognate DNA-binding site is described. MarA consists of two similar subdomains, each containing a helix-turn-helix DNA-binding motif. The two recognition helices of the motifs are inserted into adjacent major groove segments on the same face of the DNA but are separated by only 2...

Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC) class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one pro...

Polyamides composed of N-methylpyrrole (Py), N-methylimidazole (Im) and N-methylhydroxypyrrole (Hp) amino acids linked by beta-alanine (beta) bind the minor groove of DNA in 1:1 and 2:1 ligand to DNA stoichiometries. Although the energetics and structure of the 2:1 complex has been explored extensively, there is remarkably less understood about 1:1 recognition beyond the initial studies on netr...

Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCGCGCGCGC)2 and d(ATATATATAT)2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. For d(ATATATATAT)2 it was concluded...

Two distinct modes of interaction of the fluorescent probe 4',6-diamidino-2-phenylindole (DAPI), depending on the sequence of DNA, have been reported in the literature. In the present study, the dynamics of solvation has been utilized to explore the binding interaction of DAPI to DNA oligomers of different sequences. Picosecond-resolved fluorescence and polarization-gated anisotropy have been u...

CD1 proteins present self- and foreign lipid Ags to activate specific T cells in the mammalian immune system. These T cells play an important role in controlling autoimmune diseases, suppression of tumor growth, and host defense against invading pathogens. Humans use five CD1 isoforms, whereas only two exist in birds. Unlike mammals' CD1, the structure of chicken CD1-2 showed a primitive lipid-...