Enzymes, catalysis

Blumenfeld L A, Burbajev D S and Davydov R M 1986 Processes of conformational relaxation in enzyme catalysis The Fluctuating Enzyme ed E R Welch (New York Wiley) pp 369-402... 

Living systems contain thousands of different enzymes As we have seen all are structurally quite complex and no sweeping generalizations can be made to include all aspects of enzymic catalysis The case of carboxypeptidase A illustrates one mode of enzyme action the bringing together of reactants and catalytically active functions at the active site... 

Enzymatic resolution (Section 7 13) Resolution of a mixture of enantiomers based on the selective reaction of one of them under conditions of enzyme catalysis... 

Elucidating Mechanisms for the Inhibition of Enzyme Catalysis An inhibitor interacts with an enzyme in a manner that decreases the enzyme s catalytic efficiency. Examples of inhibitors include some drugs and poisons. Irreversible inhibitors covalently bind to the enzyme s active site, producing a permanent loss in catalytic efficiency even when the inhibitor s concentration is decreased. Reversible inhibitors form noncovalent complexes with the enzyme, thereby causing a temporary de-... 

Enzyme catalysis Enzyme electrode Enzyme immobilization Enzyme immunoassay Enzyme inhibitors... 

Enzyme technology Enzyme treatment Enzymic catalysis EOD... 

These bonds are sufficiendy strong to direct molecular iateractions such as the attraction between an enzyme and its substrate, but sufficiently weak to be reversibly made and broken, as ia enzyme catalysis (11). 

Fermentation. The term fermentation arose from the misconception that black tea production is a microbial process (73). The conversion of green leaf to black tea was recognized as an oxidative process initiated by tea—enzyme catalysis circa 1901 (74). The process, which starts at the onset of maceration, is allowed to continue under ambient conditions. Leaf temperature is maintained at less than 25—30°C as lower (15—25°C) temperatures improve flavor (75). Temperature control and air diffusion are faciUtated by distributing macerated leaf in layers 5—8 cm deep on the factory floor, but more often on racked trays in a fermentation room maintained at a high rh and at the lowest feasible temperature. Depending on the nature of the leaf, the maceration techniques, the ambient temperature, and the style of tea desired, the fermentation time can vary from 45 min to 3 h. More highly controlled systems depend on the timed conveyance of macerated leaf on mesh belts for forced-air circulation. If the system is enclosed, humidity and temperature control are improved (76). 

Fig. 2. Enzyme catalysis by glycinaminde nbonucleotide transfomiylase (GAR TFase). (a) Transfer of the formyl group from (13) to (12) to form 2-(formylamino)-A/-(5-0-phosphono-P-D-ribofuranosyl acetamide [349-34-8] (14) and (b) multisubstrate inhibitor (15).

In this section the applications of QM-MM methods to three enzymes are presented with the intention of illustrating the techniques that are employed to simulate enzyme catalysis. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

The QM-MM study of TIM was the first illustration of the potential of these methods for studying enzyme catalysis and has served as a reference for the protocol needed for subsequent studies of enzyme reactions. 

AR Fersht. Structure and Mechanism in Protein Science A Guide to Enzyme Catalysis and Protein Folding. New York WFl Freeman, 1999. 

In this chapter we shall illustrate some fundamental aspects of enzyme catalysis using as an example the serine proteinases, a group of enzymes that hydrolyze peptide bonds in proteins. We also examine how the transition state is stabilized in this particular case. 

Thomas, P.G., Russel, A.J., Fersht, A. Tailoring the pH dependence of enzyme catalysis using protein engineering. Nature 318 375-376, 1985. 

Many examples are known in the field of enzyme catalysis, the groups HA and B both being situated in the active site of the enzyme. 

This idea also helps to explain some of the mystery surrounding the enormous catalytic power of enzymes In enzyme catalysis, precise orientation of catalytic residues comprising the active site is necessary for the reaction to occur substrate binding induces this precise orientation by the changes it causes in the protein s conformation. 

Enigmas abound in the world of enzyme catalysis. One of these surrounds the discussion of how the rate enhancement by an enzyme can be best expressed. Notice that the nncatalyzed conversion of a substrate S to a product P is usually a simple first-order process, described by a first-order rate constant... 

Enzyme catalysis requires that Kj- < Kg. According to transition-state theory (see references at end of chapter), the rate constants for the enzyme-catalyzed k ) and uncatalyzed k reactions can be related to Kg and K by ... 

Clearly, proximity and orientation play a role in enzyme catalysis, but there is a problem with each of the above comparisons. In both cases, it is impossible to separate true proximity and orientation effects from the effects of entropy loss when molecules are brought together (described the Section 16.4). The actual rate accelerations afforded by proximity and orientation effects in Figures 16.14 and 16.15, respectively, are much smaller than the values given in these figures. Simple theories based on probability and nearest-neighbor models, for example, predict that proximity effects may actually provide rate increases of only 5- to 10-fold. For any real case of enzymatic catalysis, it is nonetheless important to remember that proximity and orientation effects are significant. 

Lolis, E., and Petsko, G., 1990. Transition-state analogues in protein crystallography Probes of the structural source of enzyme catalysis. Annual Review of Biochemistry 59 597—630. 

Gerlt, J. A., Kreevoy, M. M., Cleland, W. W., and Frey, P. A., 1997. Understanding enzymic catalysis The importance of short, strong hydrogen bonds. Chemistry and Biology 4 259-267. 

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