Meister model

The above data, along with other data from Meister s group (102, 103), provided the basis for computer modeling studies (104) of the active site conformations of substrates and intermediates in the glutamine synthetase reaction. The conclusions are that both structures II and III are in the reaction mechanism. 

Another interesting point explored in detail by Wedler and Horn 87) is that the apparent binding constant of methionine sulfoximine for the irreversible inhibition is 100 jxM compared to 1.5 fiM for direct binding to the enzyme. This leads to speculation that perhaps methionine sulfoximine can bind to the enzyme in two conformations one for competitive binding that does not lead to irreversible inhibition, while another conformer binds in a different manner, producing the irreversible inhibition. The proposal from computer modeling studies of Gass and Meister 104) is that one conformation is responsible for both, but recent data open the door for further study and speculation. 

Joshi, R.K., Meister, Th., Scapozza, L. and Ha, T.-K. (1993). Development of New Molecular Descriptors Using Conformational Energies from Quantum Calculations and Their Application in QSAR Analysis. In Trends in QSAR and Molecular Modelling 92 (Wermuth, C.G., ed.), ESCQM, Leiden (The Netherlands), pp. 362-363. 

R. Breslow, Artificial enzymes and enzyme models, in Advances in Enzymology and Related Areas of Molecular Biology, A. Meister (Ed.) John Wiley Sons, Inc., 58, 1-60, 1986. 

The technique for human error-rate prediction (THERP) [ Swain and Guttmann, 1980] is a widely applied human reliability method (Meister, 1984] used to predict human error rates (i.e., probabilities) and the consequences of human errors. The method relies on conducting a task analysis. Estimates of the likelihood of human errors and the likelihood that errors will be undetected are assigned to tasks from available human performance databases and expert judgments. The consequences of uncorrected errors are estimated from models of the system. An event tree is used to track and assign conditional probabilities of error throughout a sequence of activities. 

In 1968 Ronzio and Meister had already developed a model for GS inhibition by methionine sulfoximine (MSO) [21]. They postulated that MSO inhibits GS in two steps. The first step is reversible when the inhibitor competes with glutamate at the binding site. In the second step the substrate analogue is phosphorylated (Scheme 6.3.2) and then irreversibly bound to the enzyme. Manderscheid and Wild [22] confirmed the two-step hypothesis using L-phosphinothricin in their inhibition studies with GS from wheat. They found that the phosphorylated phosphinothricin was irreversibly bound to the enzyme. Furthermore, they concluded that each subunit of the enzyme is able to bind one molecule of phosphinothricin. 

Breslow, R., Artificial enzymes and enzyme models. In Meister, A. (Ed.), Advances in Enzymologyand Related... 

As a matter of fact, by combining the molecular network theory and the tube model, Meister (1989) advanced an idea to predict a gradual transition from 3.4-power to 3.0-power dependence of r] on M as M/M ratio increases. Specifically, Meister obtained an expression for a 3.5-power dependence of jjq on... 

For very high molecular weight polymers, Meister (1989) modified the prediction of jjo by the tube model to obtain the following expression ... 

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