Porous exfoliated poly(ε-caprolactone)/clay nanocomposites:Preparation, structure, and properties

Disclosed are the cna gene and cna-derived nucleic acid segments from Staphylococcus aureus, and DNA segments encoding cna from related bacteria. Also disclosed are Col binding protein (CBP) compositions and methods of use. The CBP protein and antigenic epitopes derived therefrom are contemplated for use in the treatment of pathological infections, and in particular, for use in the prevention of bacterial adhesion to Col. DNA segments encoding these proteins and anti-(Col binding protein) antibodies will also be of use in various screening, diagnostic and therapeutic applications including active and passive immunization and methods for the prevention of bacterial colonization in an animal such as a human. These DNA segments and the peptides derived therefrom are contemplated for use in the preparation of vaccines and, also, for use as carrier proteins in vaccine formulations, and in the formulation of compositions for use in the prevention of S. aureus infection.U

Collagen binding protein compositions and methods of use

Disclosed are the cna gene and cna-derived nucleic acid segments from Staphylococcus aureus, and DNA segments encoding cna from related bacteria. Also disclosed are Col binding protein (CBP) compositions and methods of use. The CBP protein and antigenic epitopes derived therefrom are contemplated for use in the treatment of pathological infections, and in particular, for use in the prevention of bacterial adhesion to Col. DNA segments encoding these proteins and anti-(Col binding protein) antibodies will also be of use in various screening, diagnostic and therapeutic applications including active and passive immunization and methods for the prevention of bacterial colonization in an animal such as a human. These DNA segments and the peptides derived therefrom are contemplated for use in the preparation of vaccines and, also, for use as carrier proteins in vaccine formulations, and in the formulation of compositions for use in the prevention of S. aureus infection.U

Asymmetric Structure of the Yeast F1 ATPase in the Absence of Bound Nucleotides*

The crystal structure of nucleotide-free yeast F1 ATPase has been determined at a resolution of 3.6 Å. The overall structure is very similar to that of the ground state enzyme. In particular, the βDP and βTP subunits both adopt the closed conformation found in the ground state structure despite the absence of bound nucleotides. This implies that interactions between the γ and β subunits are as important as nucleotide occupancy in determining the conformational state of the β subunits. Furthermore, this result suggests that for the mitochondrial enzyme, there is no state of nucleotide occupancy that would result in more than one of the β subunits adopting the open conformation. The adenine-binding pocket of the βTP subunit is disrupted in the apoenzyme, suggesting that the βDP subunit is responsible for unisite catalytic activity

Crystal Structures of Mutant Forms of the Yeast F1 ATPase Reveal Two Modes of Uncoupling*

The mitochondrial ATP synthase couples the flow of protons with the phosphorylation of ADP. A class of mutations, the mitochondrial genome integrity (mgi) mutations, has been shown to uncouple this process in the yeast mitochondrial ATP synthase. Four mutant forms of the yeast F1 ATPase with mgi mutations were crystallized; the structures were solved and analyzed. The analysis identifies two mechanisms of structural uncoupling: one in which the empty catalytic site is altered and in doing so, apparently disrupts substrate (phosphate) binding, and a second where the steric hindrance predicted between γLeu83 and βDP residues, Leu-391 and Glu-395, located in Catch 2 region, is reduced allowing rotation of the γ-subunit with less impedance. Overall, the structures provide key insights into the critical interactions in the yeast ATP synthase involved in the coupling process

Autoantibody-catalyzed hydrolysis of amyloid ß peptide

We describe IgM class human autoantibodies that hydrolyze amyloid ß peptide 1-40 (Aß40). A monoclonal IgM from a patient with Waldenström's macroglobulinemia hydrolyzed Aß40 at the Lys-28 - Gly-29 bond and Lys-16 - Ala-17 bonds. The catalytic activity was inhibited stoichiometrically by an electrophilic serine protease inhibitor. Treatment with the catalytic IgM blocked the aggregation and toxicity of Aß40 in neuronal cell cultures. IgMs purified from the sera of patients with Alzheimer disease (AD) hydrolyzed Aß40 at rates superior to IgMs from age-matched humans without dementia. IgMs from non-elderly humans expressed the least catalytic activity. The reaction rate was sufficient to afford appreciable degradation at physiological Aß and IgM concentrations found in peripheral circulation. Increased Aß concentrations in the AD brain are thought to induce neurodegenerative effects. Peripheral administration of Aß binding antibodies has been suggested as a potential treatment of AD. Our results suggest that catalytic IgM autoantibodies can help clear Aß, and they open the possibility of using catalytic Abs for AD immunotherapy. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Structure of the c(10) ring of the yeast mitochondrial ATP synthase in the open conformation

The proton pore of the F1Fo ATP synthase consists of a ring of c subunits, which rotates, driven by downhill proton diffusion across the membrane. An essential carboxylate side chain in each subunit provides a proton-binding site. In all the structures of c-rings reported to date, these sites are in a closed, ion-locked state. Structures are here presented of the c10 ring from Saccharomyces cerevisiae determined at pH 8.3, 6.1 and 5.5, at resolutions of 2.0 Å, 2.5 Å and 2.0 Å, respectively. The overall structure of this mitochondrial c-ring is similar to known homologs, except that the essential carboxylate, Glu59, adopts an open extended conformation. Molecular dynamics simulations reveal that opening of the essential carboxylate is a consequence of the amphiphilic nature of the crystallization buffer. We propose that this new structure represents the functionally open form of the c subunit, which facilitates proton loading and release