Enzymes hydrophobic interactions

Chapter 5 also demonstrates that a combination of Lewis-acid catalysis and micellar catalysis can lead to accelerations of enzyme-like magnitudes. Most likely, these accelerations are a consequence of an efficient interaction between the Lewis-acid catalyst and the dienophile, both of which have a high affinity for the Stem region of the micelle. Hence, hydrophobic interactions and Lewis-acid catalysis act cooperatively. Unfortunately, the strength of the hydrophobic interaction, as offered by the Cu(DS)2 micellar system, was not sufficient for extension of Lewis-acid catalysis to monodentate dienophiles. 

Effect of Temperature and pH. The temperature dependence of enzymes often follows the rule that a 10°C increase in temperature doubles the activity. However, this is only tme as long as the enzyme is not deactivated by the thermal denaturation characteristic for enzymes and other proteins. The three-dimensional stmcture of an enzyme molecule, which is vital for the activity of the molecule, is governed by many forces and interactions such as hydrogen bonding, hydrophobic interactions, and van der Waals forces. At low temperatures the molecule is constrained by these forces as the temperature increases, the thermal motion of the various regions of the enzyme increases until finally the molecule is no longer able to maintain its stmcture or its activity. Most enzymes have temperature optima between 40 and 60°C. However, thermostable enzymes exist with optima near 100°C. 

Owing to the weak hydrophobicity of the PEO stationary phases and reversibility of the protein adsorption, some advantages of these columns could be expected for the isolation of labile and high-molecular weight biopolymers. Miller et al. [61] found that labile mitochondrial matrix enzymes — ornitine trans-carbomoylase and carbomoyl phosphate synthetase (M = 165 kDa) could be efficiently isolated by means of hydrophobic interaction chromatography from the crude extract. 

Kim CU, Lew W, Wilhams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119 681-690... 

In most cases the initial interactions between the enzyme and the substrate molecule (i.e., the initial binding event) are noncovalent, making use of hydrogen bonding, electrostatic, hydrophobic interactions, and van der Waals forces to effect binding. 

Among its inhibitors are methotrexate (MTX), trimethoprim, and other derivatives of pyrimidines, triazines, pteridines, and related heterocyclic compounds. Some of these inhibitors, such as MTX, bind more tightly to Escherichia coli enzyme than does the substrate dihydrofolate. This fact has been attributed to ion-pair formation between protonated MTX and a negative carboxyl, presumably Asp-27, as well as to hydrophobic interactions.33... 

The active site of an enzyme is generally a pocket or cleft that is specialized to recognize specific substrates and catalyze chemical transformations. It is formed in the three-dimensional structure by a collection of different amino acids (active-site residues) that may or may not be adjacent in the primary sequence. The interactions between the active site and the substrate occur via the same forces that stabilize protein structure hydrophobic interactions, electrostatic interactions (charge-charge), hydrogen bonding, and van der Waals interactions. Enzyme active sites do not simply bind substrates they also provide catalytic groups to facilitate the chemistry and provide specific interactions that stabilize the formation of the transition state for the chemical reaction. 

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