Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting >50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylatio...

Allostery pervades macromolecular function and drives cooperative binding of ligands to macromolecules. To decipher the mechanisms of cooperative ligand binding it is necessary to define at a microscopic level the structural and thermodynamic consequences of binding of each ligand to its allosterically coupled site(s). However, dynamic sampling of alternative conformations (microstates) in allo...

The tetracycline antiporter TetA(B) is a member of the Major Facilitator Superfamily which confers tetracycline resistance to cells by coupling the efflux of tetracycline to the influx of protons down their chemical potential gradient. Although it is a medically important transporter, its structure has yet to be determined. One possibility for why this has proven difficult is that the transport...

Selective complexation of metal ions represents a powerful tool for the development versatile supramolecular architectures. While research in field molecular devices and machinery is sophisticated, selective formation complexes not prevalent polymer chemistry. Thus, implementation orthogonal binding concepts into polymeric matrix presented. In this context, an end-functionalized poly(N-isopropy...

0022-2836/$ see front matter q 2004 E Abbreviations used: AcWL5, acet isothermal titration calorimetry; DS scanning calorimetry; TM, transmem palmitoyl-oleoyl-phosphocholine. E-mail address of the correspond [email protected] The hexapeptide acetyl-Trp-Leu5 (AcWL5) has the remarkable ability to assemble reversibly and spontaneously into b-sheets on lipid membranes as a result of monomer partit...