DNA Damage Accelerates G-Quadruplex Folding in a Duplex-G-Quadruplex-Duplex Context.

Molecular details for the impact of DNA damage on folding of potential G-quadruplex sequences (PQSs) to noncanonical DNA structures involved in gene regulation are poorly understood. Here, the effects of DNA base damage and strand breaks on PQS folding kinetics were studied in the context of the promoter sequence embedded between two DNA duplex anchors, termed a duplex-G-quadruplex-duplex (DGD) motif. This DGD scaffold imposes constraints on the PQS folding process that more closely mimic those found in genomic DNA.

DNA Damage Accelerates G-Quadruplex Folding in a Duplex-G-Quadruplex-Duplex Context.

Molecular details for DNA damage impact on the folding of potential G-quadruplex sequences (PQS) to non-canonical DNA structures that are involved in gene regulation are poorly understood. Here, the effects of DNA base damage and strand breaks on PQS folding kinetics were studied in the context of the promoter sequence embedded between two DNA duplex anchors, referred to as a duplex-G-quadruplex-duplex (DGD) motif. This DGD scaffold imposes constraints on the PQS folding process that more closely mimic those found in genomic DNA.

Interactions of alkyltin salts with biological dithiols: dealkylation and induction of a regular beta-turn structure in peptides.

Organotin compounds specifically target vicinal dithiols, thereby inhibiting the function of essential enzymes. Here, we present the NMR binding studies of trimethyltin (TMT) and dimethyltin (DMT) chlorides with a linear peptide (ILGCWCYLR) derived from the membrane protein stannin (SNN). We show that this peptide is able to dealkylate TMT and bind DMT, adopting a stable type-I beta-turn conformation.

Structure and orientation of pardaxin determined by NMR experiments in model membranes.

Pardaxins are a class of ichthyotoxic peptides isolated from fish mucous glands. Pardaxins physically interact with cell membranes by forming pores or voltage-gated ion channels that disrupt cellular functions. Here we report the high-resolution structure of synthetic pardaxin Pa4 in sodium dodecylphosphocholine micelles, as determined by (1)H solution NMR spectroscopy.

Dealkylation of organotin compounds by biological dithiols: toward the chemistry of organotin toxicity.

In this Communication, we report evidence for the dealkylation of trialkyltin compounds by a short linear peptide extracted from a small membrane protein (stannin) involved in cellular apoptosis and containing a CXC motif. We show that (a) organotin binding induces the formation of a beta-turn in the linear peptide, (b) both cysteines are necessary for the dealkylation reaction, and (c) stable 1:1 complexes are formed between the peptide and diorganotins that can be observed by ESI-MS. Organotin degradation by biological dithiols may be responsible for both the delayed activity of these toxins in humans and the organotin resistance mechanisms in bacteria.

Overexpression, purification, and characterization of recombinant Ca-ATPase regulators for high-resolution solution and solid-state NMR studies.

Phospholamban (PLB) and Sarcolipin (SLN) are integral membrane proteins that regulate muscle contractility via direct interaction with the Ca-ATPase in cardiac and skeletal muscle, respectively. The molecular details of these protein-protein interactions are as yet undetermined. Solution and solid-state NMR spectroscopies have proven to be effective tools for deciphering such regulatory mechanisms to a high degree of resolution; however, large quantities of pure recombinant protein are required for these studies.