Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex.

WDR5 is a core component of SET1-family complexes that achieve transcriptional activation via methylation of histone H3 on Nzeta of Lys4 (H3K4). The role of WDR5 in the MLL1 complex has recently been described as specific recognition of dimethyl-K4 in the context of a histone H3 amino terminus; WDR5 is essential for vertebrate development, Hox gene activation and global H3K4 trimethylation. We report the high-resolution X-ray structures of WDR5 in the unliganded form and complexed with histone H3 peptides having unmodified and mono-, di- and trimethylated K4, which together provide the first comprehensive analysis of methylated histone recognition by the ubiquitous WD40-repeat fold.

A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias.

DNA gyrase is unique among type II topoisomerases in that its DNA supercoiling activity is unidirectional. The C-terminal domain of the gyrase A subunit (GyrA-CTD) is required for this supercoiling bias. We report here the x-ray structure of the Escherichia coli GyrA-CTD (Protein Data Bank code 1ZI0).

Synthesis of a metallopeptide-PNA conjugate and its oxidative cross-linking to a DNA target.

A nickel(II)-PNA bioconjugate was prepared by formation of a salicylaldimine complex with the amino terminus of a peptide-PNA hybrid with the sequence Arg-His-Gly-[TACCTAGCAT]PNA-Arg-CONH2. Hybridization to complementary oligodeoxynucleotides was demonstrated, and covalent adduct formation was observed upon addition of KHSO5 as oxidant. In the absence of PNA, the reactivity of the phenolic radical generated as an intermediate was found to be G >> T >> C, A; by inclusion of the PNA delivery agent, cross-links between the two oligomers could be observed with T and C bases in the vicinity of the nickel complex, although G was still the most reactive site.