Reverse gyrases are topoisomerases that introduce positive supercoils into DNA in an ATP-dependent reaction. They consist of a helicase domain and a topoisomerase domain that closely cooperate in catalysis. The mechanism of the functional cooperation of these domains has remained elusive. Recent studies have shown that the helicase domain is a nucleotide-regulated conformational switch that alt...

A two-stranded alpha-helical coiled coil was prepared having a Cys 4 metal-binding site within its hydrophobic interior. The addition of Cd2+ results in the incorporation of 2 equiv of metal ion, which is accompanied by a conformational change of the peptide, as observed by circular dichroism (CD) spectroscopy. Isothermal titration calorimetry (ITC) shows that the addition of Cd2+ is accompanie...

Small oligomers formed early along human islet amyloid polypeptide (hIAPP) aggregation is responsible for the cell death in Type II diabetes. The epigallocatechin gallate (EGCG), a green tea extract, was found to inhibit hIAPP fibrillation. However, the inhibition mechanism and the conformational distribution of the smallest hIAPP oligomer - dimer are mostly unknown. Herein, we performed extens...

Single-stranded DNA (ssDNA) is characterized by high conformational flexibility that allows these molecules to adopt a variety of conformations. Here we used native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy to show that cytosine methylation at CpG sites affects the conformational flexibility of short ssDNA m...

Nucleic acid molecules can adopt a variety of structures and exhibit a large degree of conformational flexibility to fulfill their various functions in cells. Here we describe the use of Pulsed Electron-Electron Double Resonance (PELDOR or DEER) to investigate nucleic acid molecules where two cytosine analogs have been incorporated as spin probes. Because these new types of spin labels are rigi...

Structural DNA nanotechnology, the assembly of rigid 3D structures of complex yet precise geometries, has recently been used to design dynamic, mechanically compliant nanostructures with tunable equilibrium conformations and conformational distributions. Here we use coarse-grained molecular dynamics simulations to provide insights into the conformational dynamics of a set of mechanically compli...

The TREX enzymes process DNA as the major 3'-->5' exonuclease activity in mammalian cells. TREX2 and TREX1 are members of the DnaQ family of exonucleases and utilize a two metal ion catalytic mechanism of hydrolysis. The structure of the dimeric TREX2 enzyme in complex with single-stranded DNA has revealed binding properties that are distinct from the TREX1 protein. The TREX2 protein undergoes ...

The extreme 3'-ends of human telomeres consist of 150-250 nucleotides of single-stranded DNA sequence together with associated proteins. Small-molecule ligands can compete with these proteins and induce a conformational change in the DNA to a four-stranded quadruplex arrangement, which is also no longer a substrate for the telomerase enzyme. The modified telomere ends provide signals to the DNA...

Nucleic acid-based biosensors for the detection of specific proteins combine typical programmability synthetic DNA systems with artificially controlled DNA-protein communication. The high-affinity interaction between a target protein and ligand, such as an aptamer sequence, or double stranded domain, small peptide, is paired nature-mimicking molecular mechanism allowing probing, processing, tra...