The prime mechanism by which p53 acts as a tumor suppressor is as a transcription factor regulating the expression of diverse downstream genes. The DNA-binding domain of p53 (p53DBD) interacts with defined DNA sites and is the main target for mutations in human primary tumors. Here, we show that the CWWG motif, found in the center of each consensus p53 half-site, is a key player in p53/DNA inte...

It is shown that the modulation in the negative cooperativity of ligand binding by another, competing ligand that binds noncooperatively is accounted for exclusively by the ligand-induced sequential model. It is therefore suggested that whenever such a phenomenon is observed it argues strongly in favor of the sequential model. The advantages and limitations of this approach are evaluated. The b...

We examined the mechanism by which cyclic AMP-dependent protein kinase (PK) stimulates the calcium pump of cardiac sarcoplasmic reticulum vesicles. The Ca dependence of calcium uptake rates by 30 /ig/ml canine cardiac sarcoplasmic reticulum was measured at 25 °C in 120 mM KCl, 40 mM histidine buffer (pH 6.8), 5 mM MgATP, and an ATP-regenerating system (75 fig/ml pyruvate kinase + 5 mM phosphoen...

BACKGROUND The affinities of DNA binding proteins for target sites can be used to model the regulation of gene expression. These proteins can bind to DNA cooperatively, strongly impacting their affinity and specificity. However, current methods for measuring cooperativity do not provide the means to accurately predict binding behavior over a wide range of concentrations. METHODS We use standa...

Cooperativity is one of the most important properties of molecular interactions in biological systems. It is the ability to influence ligand binding at one site of a macromolecule by previous ligand binding at another site of the same molecule. As a consequence, the affinity of the macromolecule for the ligand is either decreased (negative cooperativity) or increased (positive cooperativity). O...

Rhodes, Samhita S., Kristina M. Ropella, Amadou K. S. Camara, Qun Chen, Matthias L. Riess, Paul S. Pagel, and David F. Stowe. Ischemia-reperfusion injury changes the dynamics of Ca contraction coupling due to inotropic drugs in isolated hearts. J Appl Physiol 100: 940–950, 2006. First published November 10, 2005; doi:10.1152/japplphysiol.00285.2005.—Positive inotropic drugs may attenuate or exa...