Enzyme, cleft enzymes

Kemp s Acid Enzyme-Cleft and Self-Replication Models... 

Kemp s Acid Enzyme-Cleft and Self-Replication Models 347 5.2.1 Enzyme-Cleft Models with Convergent Functional Croups... 

Enzyme-Cleft Models with Convergent Functional Croups... 

Global minimum conformations within the enzyme clefts Folded conformation with the phenyl of moiety A in close proximity to the thiazo-... 

Another interesting application of a structurally ill-defined assembly is the first efficient hydrolysis of an amide at room temperature and pH 8. When the cationic amide 15 (2 x 10 M) is mixed with anionic palmitate (2 x 10 M)at pH 8, an undefined molecular cluster is formed in which the water-stable amide (t./, > 1 yr) rapidly hydrolyzes = 3.1 min). The long-time contact of reactants, a state thought to be essential for enzyme-like reactions, can obviously not only be enforced by neighbouring group effects in rigid molecules or in complexes between enzyme clefts and substrates. It may also occur in very simple micellar-like clusters of extremely low cmc. 

Biochemical reactions take place in the hydrophobic centers of membranes or enzyme clefts. Aqueous compartments of biological cells are usually taboo media for the formation of small molecular assemblies or covalent compounds. There is, however, one notable exception, namely the formation of inclusion... 

The high resolution X-ray structural studies of the native enzyme, the enzyme-ADPR binary complex, and the enzyme-o-phenanthroline binary complex (47) have revealed that the active site zinc ion is located some 20 A below the surface of the protein at the point of convergence of two deep clefts (see the schematic representation in Fig. 6). One of these clefts has been identified as the coenzyme binding cleft (47). This cleft extends from the surface of the subunit to the zinc ion. If a model of NADH is fit to the coordinates of the ADPR binding site, then the nicotinamide ring can be oriented in such a way that it fits into a pocket adjacent to the zinc ion (47). The second deep cleft, or channel, also extends from the surface of the subunit down to the zinc ion. The inner surface of this cleft is made up of nonpolar amino acid residues contributed by both subunits. 

We will give a detailed description of recent insights obtained especially for the widely studied hexakinase enzyme, which catalyzes the phosphorylation of glucose. The phosphorylation of glucose by hexakinase has been modeled in detail by simulating the reaction events that can occur in the enzyme cleft PI. The free hexakinase enzyme molecule is... 

The shape of the enzyme cleft is clearly more complex than for the A9 desaturase and involves polar sites capable of weakly interacting with existing double bonds in the substrate at positions 9-10, 12 13, 13-14 and 15-16. A greater range of possible substrates needs to be tested before the shape and dimensions of the cleft can be more accurately defined. 

The lattice can be made to conform to the shape of the molecule which is represented. We were interested in following differences in unfolding between enzyme and enzyme-substrate (or enzyme-inhibitor) complex, c.q. between apoprotein and protein. X-ray crystallographic studies have shown that many enzymes have a cleft which can accomodate a substrate molecule. Similarly, since myoglobin has a compact... 

Figure 4 The effect of ionic strength on HI torques is plotted for a cleft enzyme model (as described in the text) with a rod-like substrate. Change in the HI are computed with respect to a similar model including HI bu without HI torques. Note that the HI torques are maximal at phy ologic ionic strength (150 mM)...

In free CDK2 the active site cleft is blocked by the T-loop and Thr 160 is buried (Figure 6.20a). Substrates cannot bind and Thr 160 cannot be phosphorylated consequently free CDK2 is inactive. The conformational changes induced by cyclin A binding not only expose the active site cleft so that ATP and protein substrates can bind but also rearrange essential active site residues to make the enzyme catalytically competent (Figure 6.20b). In addition Thr... 

Figure 5.9 Models of hexo-kinase in space-filling and wireframe formats, showing the cleft that contains the active site where substrate binding and reaction catalysis occur. At the bottom is an X-ray crystal structure of the enzyme active site, showing the positions of both glucose and ADP as well as a lysine amino acid that acts as a base to deprotonate glucose.

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