Role of active sites

Leimkiihler S, AL Stockert, K Igarashi, T Nishino, R Hille (2004) The role of active site glutamate residues in catalysis of Rhodobacter capsulatus xanthine dehydrogenase. J Biol Chem 279 40437-40444. 

Accordingly, in order to understand the roles of active sites in catalysis, we should clarify not only the intermediates but also the functions of active sites in relation to elementary processes. For this reason, it may be an interesting question whether the two reactions taking place via the same kind of intermediates occur on the same or different active sites. One good example is the isomerization of olefins via alkyl intermediates and their subsequent hydrogenation. In the Horiuti and Polanyi mechanism, complete overlapping of the intermediates, as well as the reaction routes, was tacitly assumed as described in Eq. (1). In this reaction scheme, step (1) and step ( ) are the... 

In vitro mutagenesis is used to evaluate how the individual residues are involved in enzyme catalysis this is difficult to pursue with traditional methods, such as physicochemical or chemical modification. Mutagenesis study has been successfully employed to define the role of active-site residues in AspAT. It was found that some of the active-site residues are involved in coenzyme binding, some are used for substrate recognition, and others are involved directly in catalysis. 

Atkins, W. M., and Sligar, S. G., 1988, The roles of active site hydrogen bonding in cytochrome P450 cam as revealed by site-directed mutagenesis, J. Biol. Chem., 263 18842n18849. 

Speculation about the precise roles of active-site sulfur is tempered by an appreciation of the redox versatihty and interplay of sulfur and molybdenum. This is evident from synthetic systems, where the catenation of sulfur (with attendant redox and/or ligand elaboration) and induced internal electron-transfer reactions are frequently observed. The redox interplay of Mo and S, reflected in undesirable synthetic outcomes, may prove crucial to a fifll description of enzyme behavior. see also Sulfur Inorganic Chemistry)... 

R, Olsen, J.G., McGuire, K.A., and Henriksen, A., Fatty acid synthesis. Role of active site histidines and lysine in Cys-His-His-type beta-ketoacyl-acyl carrier protein synthases, FEBS J. 273, 695-710, 2(X)6 Ryn, Y, Kim, KJ., Rosennser, C.A., and Scott, A., Decarboxylative Qaisen condensation catalyzed by in vitro selected ribozymes, Chem. Commun. 7, 1439-1441, 2006. 

Blevins and Tulinsky (1985) suggested two functions for the solvent at the chymotrypsin active site (1) solvation of the Asp—His—Ser catalytic triad, and (2) a guiding effect on the substrate in formation of the enzyme-substrate complex, provided by several waters at the end of the specificity site. X-Ray diffraction results have suggested a role of active-site water in determining the kinetics or equilibria of substrate binding for other proteins (Section IV). 

Further insight into the mechanism was provided by QM/MM analysis of the roles of active site groups on the hydroxylation step in PHBH. Qualitative information on nearby groups which significantly affect the reaction energetics can be found by a simple decomposition procedure described as a first-order perturbation analysis [13,48]. In essence, this involves the calculation of the... 

Staphylococcal nuclease (SNase) is one of the most powerful enzymes known in terms of its rate acceleration, with a catalytic rate that exceeds that of the non-enzymatic reaction by as much as 1016.211 This enzyme is a phosphodiesterase, and utilizes a Ca2+ ion for catalysis to hydrolyze the linkages in DNA and RNA. In addition to the metal ion, the active site has two Arg residues in a position to interact with the phosphoryl group, and a glutamate. X-ray structures212 215 of SNase have been solved for the wild-type enzyme and mutants, but the exact roles of active-site residues are still uncertain. SNase cleaves the 5 O-P nucleotide bond to yield a free 5 -hydroxyl group (Fig. 30). 

The step decoration obtained during spontaneous deposition of Ru on the Au(l 11) surface indicates that the steps were the active sites for the chemical reactions involving the formation of solid Ru02 species and subsequent chemical disproportionate reaction discussed above. This reveals that, for a particular concentration of the solution, the density of the steps is the main factor determining the Ru coverage. A higher density of steps or active sites can be achieved either by multiple deposition, whereby the deposited Ru islands take over the role of active sites in the deposition (see... 

The effect of pH variation and isotope (or elemental) substitution on reaction kinetics has been used in the steady state to explore the roles of active site acid/base catalysts and to attempt to define the nature of the transition state (8a, 8b, 58). Each of these methods also depends on the extent to which the rate of the chemical reaction is rate limiting in the steady state. If some other step limits the rate of steady-state turnover, then changes in the rate of the chemical reaction will be obscured. Use of pH variation or isotope effects in transient kinetic experiments has been useful in a number of cases (27), especially where it has been possible to examine directly the rate of the chemical reaction at the enzyme active site. In these cases, the effect of pH or isotope substitution can be interpreted directly in terms of the effect on a single reaction. 

FabI mechanism and role of active site residues 248... 

Lee-Robichaud, R, M.E. Akhtar, and M. Akhtar (1998). An analysis of the role of active site protic residues of cytochrome P-450s Mechanistic and mutational studies on 17a-hydroxylase-17,20-lyase (P-45017a also CYP17). Biochem. J. 330, 967-974. 

An analysis of the role of active site pro-tic residues of cytochrome P-450s Mechanistic and mutational studies on 17a-hydroxylase-... 

Role of active site aspartate and histidine residues Internal electron transfer Mechanistic studies Model studies... 

Role of Active Site Residues and Water Molecules... 

Even the best single-crystal surface cannot be perfect and will rather exhibit defects, mostly steps, and dislocations, as is evident from Fig. 2.3. In catalysis, monoatomic steps often play the role of "active sites" [2] with enhanced reactivity. An example is shown in Fig. 2.4 for the interaction of NO with a RufOOOl) surface... 

These examples illustrate not only the role of active sites but also how complex their role is for macroscopic kinetics. This leads us to the general problem of how to define catalytic activity. 

Chuiko, A.A. Surface Chemistry of S/O2, Nature and Role of Active Sites in Adsorption and Chemisorption Processes Thesis Diss. Doct. Chem. Kiev, 1971. (In Russian). 

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