Functional active site models

An interesting functional active-site model system for prostaglandin H synthase has recently... 

In the second part, selected immobilized structural and spectroscopic active site models will be discussed and aspects of characterization and analytics of immobilized transition metal complexes will be exemplarily disclosed. Typical techniques include spectroscopic methods addressing the immobilized biomimetic species and determination of metal ion leaching and active site integrity, for example, by selective extraction of the intact biomimetic metal complex - the prosthetic group - from the matrix - the apoenzyme (prosthetic group extraction). The third section gives a short overview of the elementary reaction steps in the catalytic processes and their observation on solid matrixes. Selected immobilized biomimetic functional active site models will be discussed in detail in the last section. 

Bray, M. R., and R. J. Deeth. 1996. A density functional study of active site models of xantine oxidase. Inorganic Chemistry 35, 5720. 

De Gioia, L., Fantucci, P., Guigliarelli, B. and Bertrand, P. (1999a) Ni-Fe hydrogenases A density functional theory study of active site models. Inorg. Chem., 38, 2658-62. 

Figure 19. RH values observed for the efflorescence of ammonium sulfate (120 sec residence time) by heterogeneous nucleation as a function of mode diameter of the inclusions for corundum ( ) and hematite ( ). The hnes show F = 0.50 of the optimized fit to the active site model (Eqn. 24). Right axes show saturation ratios, S, of the aqueous phase with respect to crystalline ammonium sulfate and salt mole fractions, x, of the aqueous phase, as calculated from the model of Clegg et al. (1998) when assuming equihbrium between RH and water activity and omitting Kelvin effects. Adapted from Martin et al. (2001). Used by permission of the American Geophysical Unioa...

How can a theoretical method decide between proposed mechanisms, and how can the origin of the enzymatic power be identified This review will try to answer these questions for one particular theoretical approach, the one where an active site model is treated by accurate quantum mechanical (QM) methods. The main idea in the QM active site approach is to make sure that the computational results have the required accuracy. During the last decade the accuracy of density functional methods (DFT) has been dramatically improved, and in particular the hybrid B3LYP functional has achieved a remarkable accuracy [8, 9]. The use of DFT has also made it possible to treat dramatically larger molecular systems than can be done with conventional wave-function methods of similar accuracy. In spite of this important development, DFT models have usually been limited to 50-60 atoms, but more recently systems with more than 100 atoms have been treated efficiently. Still, even 100 atoms is a very small part of the total number of 8,300 atoms in yeast ODCase, not counting hydrogens or surrounding water molecules. Thus a very severe selection has to be made when the enzyme model is set up, and an important task is to select the residues required to solve the mechanism and to analyze all important contributions. 

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