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Catalytic Power (catalytic + power)
Selected AbstractsCatalytic mechanism and substrate selectivity of aldo-keto reductases: Insights from structure-function studies of Candida tenuis xylose reductaseIUBMB LIFE, Issue 9 2006Regina Kratzer Abstract Aldo-keto reductases (AKRs) constitute a large protein superfamily of mainly NAD(P)-dependent oxidoreductases involved in carbonyl metabolism. Catalysis is promoted by a conserved tetrad of active site residues (Tyr, Lys, Asp and His). Recent results of structure-function relationship studies for xylose reductase (AKR2B5) require an update of the proposed catalytic mechanism. Electrostatic stabilization by the ,-NH3+ group of Lys is a key source of catalytic power of xylose reductase. A molecular-level analysis of the substrate binding pocket of xylose reductase provides a case of how a very broadly specific AKR achieves the requisite selectivity for its physiological substrate and could serve as the basis for the design of novel reductases with improved specificities for biocatalytic applications. iubmb Life, 58: 499-507, 2006 [source] An analysis of all the relevant facts and arguments indicates that enzyme catalysis does not involve large contributions from nuclear tunnelingJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 7 2010Shina C. L. Kamerlin Abstract Enzymatic reactions are crucial toward controlling and performing most life processes, and, as such, understanding how they really work has both fundamental and practical importance. Thus, one of the major current challenges of biophysics involves understanding the origin of the enormous catalytic power of enzymes, an issue that is still not widely understood and remains controversial within the scientific community. Several proposals have been put forth to try to explain the origin of enzyme catalysis, one of which is the idea that enzyme catalysis involves special factors such as nuclear quantum mechanical (NQM) effects, and, in particular, nuclear tunneling. Here, we will discuss both the factors for and against this proposition, and demonstrate that an analysis of all the relevant facts and arguments seems to establish that enzyme catalysis does not involve large contributions from nuclear tunneling. Copyright © 2010 John Wiley & Sons, Ltd. [source] Non-aqueous reverse micelles media for the SNAr reaction between 1-fluoro-2,4-dinitrobenzene and piperidine,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2006N. Mariano Correa Abstract The kinetics of the nucleophilic aromatic substitution (SNAr) reaction between 1-fluoro-2,4- dinitrobenzene (FDNB) and piperidine (PIP) in ethylene glycol (EG)/ sodium bis (2-ethyl-1-hexyl) sulfosuccinate (AOT)/n -heptane and dimethylformamide (DMF)/AOT/n -heptane non-aqueous reverse micelle systems is reported. EG and DMF were used as models for hydrogen bond donor (HBD) and non-hydrogen bond donor (non-HBD) polar solvents, respectively. The reaction was found not to be base catalyzed in these media. A mechanism to rationalize the kinetic results is proposed in which both reactants may be distributed between the two environments. The distribution constants of FDNB between the organic and each micellar pseudophases were determined by an independent fluorescence method. These results were used to evaluate the amine distribution constant and the intrinsic second-order rate coefficient of the SNAr reaction in the interface. The reaction was also studied in the pure solvents EG and DMF for comparison. The results in EG/AOT/n -heptane at Ws,=,2 give similar kinetic profiles than in water/AOT/n -hexane at W,=,10. With these HBD solvents, the interface saturation by the substrate is reached at around the same value of [AOT] and the intrinsic second-order rate coefficient in the interface, k,b, has comparable values. On the other hand, when DMF is used as a polar non-HBD solvent, the intrinsic second-order rate constant increases by a factor of about 200 as compared to the values obtained using HBD solvents as a polar core. It is concluded that higher catalytic power is obtained when non-HBD solvents are used as polar solvent in the micelle interior. Copyright © 2006 John Wiley & Sons, Ltd. [source] On the Generation of Catalytic Antibodies by Transition State AnaloguesCHEMBIOCHEM, Issue 4 2003Montserrat Barbany Abstract The effective design of catalytic antibodies represents a major conceptual and practical challenge. It is implicitly assumed that a proper transition state analogue (TSA) can elicit a catalytic antibody (CA) that will catalyze the given reaction in a similar way to an enzyme that would evolve (or was evolved) to catalyze this reaction. However, in most cases it was found that the TSA used produced CAs with relatively low rate enhancement as compared to the corresponding enzymes, when these exist. The present work explores the origin of this problem, by developing two approaches that examine the similarity of the TSA and the corresponding transition state (TS). These analyses are used to assess the proficiency of the CA generated by the given TSA. Both approaches focus on electrostatic effects that have been found to play a major role in enzymatic reactions. The first method uses molecular interaction potentials to look for the similarity between the TSA and the TS and, in principle, to help in designing new haptens by using 3D quantitative struture,activity relationships. The second and more quantitative approach generates a grid of Langevin dipoles, which are polarized by the TSA, and then uses the grid to bind the TS. Comparison of the resulting binding energy with the binding energy of the TS to the grid that was polarized by the TS provides an estimate of the proficiency of the given CA. Our methods are used in examining the origin of the difference between the catalytic power of the 1F7 CA and chorismate mutase. It is demonstrated that the relatively small changes in charge and structure between the TS and TSA are sufficient to account for the difference in proficiency between the CA and the enzyme. Apparently the environment that was preorganized to stabilize the TSA charge distribution does not provide a sufficient stabilization to the TS. The general implications of our findings and the difficulties in designing a perfect TSA are discussed. Finally, the possible use of our approach in screening for an optimal TSA is pointed out. [source] | ||||||||||