Synthesis, solution structure, and biological evaluation of urokinase type plasminogen activator (uPA)-derived receptor binding domain mimetics.

Tumor cell migration and metastasis in cancer are facilitated by interaction of the serine protease urokinase type plasminogen activator (uPA) with its receptor uPAR (CD 87). Overexpression of uPA and uPAR in cancer tissues is associated with a high incidence of disease recurrence and early death. In agreement with these findings, disruption of the protein-protein interaction between uPAR present on tumor cells and its ligand uPA evolved as an attractive intervention strategy to impair tumor growth and metastasis.

Characterization of the molecular motions of constitutively active G protein-coupled receptors for parathyroid hormone.

The molecular mechanism of constitutive activity of the G protein-coupled receptor for human parathyroid hormone (PTH1) has been examined by molecular dynamics (MD) simulations. The single point mutations H223R, T410P, and I458R, of the PTH1 receptor result in ligand-independent receptor activation. Extensive MD simulations indicate that each of the mutations, through different mechanisms, lead to very similar conformational changes of the third intracellular loop.

Molecular characterization of the receptor-ligand complex for parathyroid hormone.

Molecular models for the interaction of parathyroid hormone (PTH) with its G-protein-coupled receptors (PTH1 and PTH2) have been developed. The proposed ligand-receptor complex is based on experimental data from spectroscopic investigations of the hormone and receptor fragments as well as theoretical structure predictions based on homology analysis with proteins of known structure. From the insight afforded by the models, biochemical and pharmacological observations can be correlated with specific molecular or atomic interactions.

Solution structure of the antitermination protein NusB of Escherichia coli: a novel all-helical fold for an RNA-binding protein.

The NusB protein of Escherichia coli is involved in the regulation of rRNA biosynthesis by transcriptional antitermination. In cooperation with several other proteins, it binds to a dodecamer motif designated rrn boxA on the nascent rRNA. The antitermination proteins of E.

Use of the Golden Section search method to estimate the parameters of the Monod model employing spread-sheets.

An alternative procedure to obtain the parameters of Monod's growth model in batch culture is presented. It is based on the integral kinetic analysis methodology, employs a one-dimensional Golden Section search optimization method and is implemented on a spread-sheet programme. The procedure is discussed in detail and is illustrated by analysis of batch substrate consumption data by an aerobic bacterial consortium.