A recent article of Johnson and Goody (Biochemistry, 2011;50:8264-8269) described the almost-100-years-old paper of Michaelis and Menten. Johnson and Goody translated this classic article and presented the historical perspectiveto one of incipient enzyme-reaction data analysis, including a pioneering global fit of the integrated rate equation in its implicit form to the experimental time-course data. They reanalyzed these data, although only numerical techniques were used to solve the model equations. However, there isalso the still little known algebraic rate-integration equation in a closed form that enables direct fitting of the data. Therefore, in this commentary, Ibriefly present the integral solution of the Michaelis-Menten rate equation, which has been largely overlooked for three decades. This solution is expressed in terms of the Lambert W function, and I demonstrate here its use for global nonlinear regression curve fitting, as carried out with the original time-course dataset of Michaelis and Menten.
COBISS.SI-ID: 29896921
It was found that polymorphisms in nucleotide excision repair pathway influence the efficacy and toxicity of platinum-based chemotherapy in patients with malignant mesothelioma.
COBISS.SI-ID: 28755417
17beta-Hydroxysteroid dehydrogenase from the filamentous fungus Cochliobolus lunatus (17beta-HSDcl) is currently the only fungal HSD member that has been described and represents one of the model enzymes ofthe cP1 classical subfamily of NADPH dependent SDR enzymes. A thorough crystallographic analysis has been performed to better understand the structural aspects of this subfamily and provided insights into the evolution of the HSD enzymes. The crystal structures of the 17beta-HSDcl apo, holo and coumestrol-inhibited ternary complex, and the active site Y167F mutant reveal subtle conformational differences in the substrate-binding loop that likely modulate the catalytic activity of 17beta-HSDcl. Coumestrol, a plant-derived non-steroidal compound with estrogenic activity, inhibits 17beta-HSDcl (IC50, 2.8 mM; at 100 muM substrate š4-estrene-3,17-dioneđ) by occupying the putativesteroid-binding site. In addition to an extensive hydrogen-bonding network, coumestrol binding is further stabilized by pi-pi stacking interactions with Tyr-212. A stopped-flow kinetic experiment clearly showed the coenzyme dissociation as the slowest step of the reaction and in addition to the low steroid solubility it prevents the accumulation of enzyme-coenzyme-steroid ternary complex formation.
COBISS.SI-ID: 28926169