Enzymes specificity, molecular configuration

A description of the pioneering work of Emil Fischer in the period around 1890, especially relating to his elucidation of the molecular configuration of glucose and aspects of his philosophical view of chemistry, has appeared. Lemieux and Spohr have looked in detail at how Fischer was led to the "lock and key" concept for enzyme specificity. An animated 386-based PC program with VGA graphics has been produced to assist visualization of the relationship between Fischer and Haworth projections of monosaccharides. ... 

Although the absolute configurations of the products are opposite to that of antiinflammatory active compounds, and the substrate specificity is rather restricted as to the steric bulkiness around the reaction center, the enzyme system of A. bronchisepticus was proved to have a unique reactivity. Thus, detailed studies on the isolated enzyme were expected to elucidate some new interesting mechanism of the new type of decarboxylation. Thus, the enzyme was purified. (The enzyme is now registered as EC 4.1.1.76.) The molecular mass was about 24kDa. The enzyme was named as arylmalonate decarboxylase (AMDase), as the rate of the decarboxylation of phenylmalonic acid was faster than that of the a-methyl derivative. ... 

The high specificity required for the analysis of physiological fluids often necessitates the incorporation of permselective membranes between the sample and the sensor. A typical configuration is presented in Fig. 7, where the membrane system comprises three distinct layers. The outer membrane. A, which encounters the sample solution is indicated by the dashed lines. It most commonly serves to eliminate high molecular weight interferences, such as other enzymes and proteins. The substrate, S, and other small molecules are allowed to enter the enzyme layer, B, which typically consist of a gelatinous material or a porous solid support. The immobilized enzyme catalyzes the conversion of substrate, S, to product, P. The substrate, product or a cofactor may be the species detected electrochemically. In many cases the electrochemical sensor may be prone to interferences and a permselective membrane, C, is required. The response time and sensitivity of the enzyme electrode will depend on the rate of permeation through layers A, B and C the kinetics of enzymatic conversion as well as the charac-... 

The observation follows that in addition io the specificity of the enzymes with respect lo reaction type and io structure of the substrate, the action is also confined to a single configuration of the substrate. If the molecular structure of (he substrate It unsymmeirical (asymmetric) and therefore... 

Phospholipases are very versatile enzymes which allow the transformation of inexpensive natural products into highly valuable compounds like specific structurally defined phospholipids, organic monophosphates or diphosphates and DAG with the natural absolute configuration. Of particular synthetic utility is PLD from bacterial sources which is able to effect the phosphoryl transfer in a water-containing biphasic system. PLD shows a wide substrate specificity for both the polar head and the alcohol acceptors as well as for the lipophilic part of the molecule. The enzyme behaves like a generic phosphodiesterase with broad substrate specificity and high transphosphatidylation ability. The molecular basis of this behavior should become clear by inspection of the three-dimensional structure and comparison with other phosphoric acid ester hydrolytic enzymes. The crystal structure of this enzyme has not been elucidated. The potential of the many different PLD from plants which show peculiar substrate specificity should allow one to expand the synthetic utility to the hydrolysis-synthesis of natural and unnatural phosphatidylinositols. 

One carries out a molecular-dynamics simulation for the reactant-state assembly at a temperature of interest for a particular example, and counts the number of configurations attained within a specific time period that are within the chosen NAC limits. Very commonly, those spedes for which large numbers of NACs are observed are found experimentally to undergo reaction between the proximate centers more rapidly than is true for spedes with a smaller population of NACs. Such studies are capable of developing a reasonably reliable catalog of the distance and orientational requirements for a broad range of reactions and thus defining some of the requirements for enzymes to promote reactions by the adjustment of distances and orientation. 

Chymotrypsin has a molecular weight of 23,000 and therefore contains nearly 200 amino acid residues. The question has been posed whether there is some other, yet unknown function inherent in the protein molecule apart from that implied in the mechanism suggested here. Our three-step reaction sequence involves an adsorption site with a specific configuration to result in the initial binding of enzyme and substrate. This absorption site must be in the right spatial configuration towards the catalytic groups (serine and histidine). 

Many drugs bind to the molecular receptors that lie in the outer membranes of each cell along the banks of the stream of life. These receptors lie in wait for molecules with the specific configuration that cause them to bind. As these molecules travel throughout the internal environment, described by Claude Bernard, they bump, fit and stick to the receptors. The receptors are analogous to keyholes into which only specific molecules fit. Drugs bump, fit, and stick to specific enzymes and other biomolecules in the symphony of life that controls our interactions with the environment. 

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