A growing body of animal studies provides evidence for potential cardioprotective effects of inhibitors of the enzyme phosphodiesterase isoform 5. Infarct size reduction by administration of phosphodiesterase 5 inhibitors was described in various experimental models of ischaemia and reperfusion. Furthermore, potential beneficial effects were demonstrated in experimental models of congestive hea...

Family 18 chitinases play key roles in a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. ...

Although protein palmitoylation is essential for targeting many important signaling proteins to the plasma membrane, the mechanism by which palmitoylation occurs is uncharacterized, since the enzyme(s) responsible for this modification remain unidentified. To study palmitoyl acyl transferase (PAT) activity, we developed an in vitro palmitoylation (IVP) assay using a fluorescently labeled substr...

Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinc...

Various pre-erythrocyte malaria vaccines are currently in clinical development, and among these is the adenovirus serotype 35-based circumsporozoite (CS) vaccine produced on PER.C6 cells. Although the immunological correlate of protection against malaria remains to be established, the CS antibody titer is a good marker for evaluation of candidate vaccines. Here we describe the validation of an ...

We show how enzymatic activity can be harnessed as a tool to fashion complex nanoand micro-scale surface topographies on biodegradable substrates. Coordinated patterning and machining are accomplished by manipulating interactions between an enzyme, substrate, and protein inhibitor. In this way, we are able to construct nanochannels, microchannels containing embedded features templated by the su...

Fig. 1 – Persistent left superior vena cava mimicking defect, bicuspid aortic valve, coarctation of aorta, coronary sinus ostial atresia, and cor triatriatum. A 81-year-old male was admitted to syncope and palpitation. He had history of hypertension and paroxysmal atrial fibrillation. Physical examination was normal. Cranial MRI was normal. 2D and 4D transthoracic echocardiography revealed norm...

The crystal structure of fiddler crab collagenase complexed with the dimeric serine protease inhibitor ecotin at 2.5 A resolution reveals an extended cleft providing binding sites for at least 11 contiguous substrate residues. Comparison of the positions of nine intermolecular main chain hydrogen bonding interactions in the cleft, with the known sequences at the cleavage site of type I collagen...

Maturation of tRNA precursors into functional tRNA molecules requires trimming of the primary transcript at both the 5’ and 3’ ends. Cleavage of nucleotides from the 3’ stem of tRNA precursors, releasing nucleotide diphosphates, is accomplished in Bacillus by a phosphate dependent exoribonuclease, Rph. The crystal structure of this enzyme from Bacillus anthracis has been solved by molecular rep...

−Viruses naturally exhibit an incredible variety of sophisticated nanostructures, which makes them ideal biological building blocks for nanoengineered material research. By mimicking their spontaneous assembly process, tremendous advances have been made towards utilizing virus and virus-like particles (VLPs) as protein cages, scaffolds, and templates for nanomaterials in the last few years. Thi...