Enzymes functional groups location

Protein phosphorylation-dephosphorylation is a highly versatile and selective process. Not all proteins are subject to phosphorylation, and of the many hydroxyl groups on a protein s surface, only one or a small subset are targeted. While the most common enzyme function affected is the protein s catalytic efficiency, phosphorylation can also alter the affinity for substrates, location within the cell, or responsiveness to regulation by allosteric ligands. Phosphorylation can increase an enzyme s catalytic efficiency, converting it to its active form in one protein, while phosphorylation of another converts it into an intrinsically inefficient, or inactive, form (Table 9—1). 

While the enzymes involved in detoxication processes are nonspecific in the classical sense of intermediary metabolism, they often have distinct specificities both for organic functional groups and for the electronic, steric, and stereochemical environments where these functional groups are located. Enzyme specificity based on organic functional groups and their environments leads to a wide diversity in the alkaloid substrates possible and therefore the products obtained from biotransformation. This section of the chapter will concentrate principally on the enzymes themselves, including general concepts of substrate specificity and mechanism. 

Almost all enzymes are proteins. They provide templates whereby reactants (substrates) can bind and are favorably oriented to react and generate the products. The locations where the substrates bind are known as active sites. Because of the specific 3D structures of the active sites, the functions of enzymes are specific that is, each particular type of enzyme catalyzes specific biochemical reactions. Enzymes speed up reactions, but they are not consumed and do not become part of the products. Enzymes are grouped into six functional classes by the International Union of Biochemists (Table 2.2). 

HMBC is a powerful tool for locating the position of a functional group within a known carbon skeleton. Oxidation of testosterone with the enzyme cytochrome P-450 (Fig. 11.29) leads to a number of hydroxylation (C-H -> C-OH) and di-hydroxylation products. One... 

Acid-catalyzed S—O fission may occur under neutral conditions under the influence of enzymic catalysis. Perhaps a functional carboxyl group obtains at the active site of the enzyme, a group which occurs in undissociated acid form and works as a powerful acid catalyst because of its location at a special hydrophobic pocket. However, we have examined other possibilities of metal-ion-catalyzed S—O fission. 

The locations of the following functional groups around the N-terminal Thr-1 of the bovine p7 subunit are consistent with the structure of an Ntn-hydrolase-active site (Fig. 3.4A). The N-terminal Thr-1 forms a hydrogen bond with Asn-104 0<5. Thr-1 Oy-H forms a hydrogen bond with Asp-59 0.<5 Arg-91 of p forms a salt bridge with Asp-56 of pi. An oxyanion hole is formed by the Tyr-88 OHof pi or Arg-99 N / of p7. A water molecule is found near Thr-1 and is replaced by substrate upon formation of the enzyme-substrate complex (Fig. 3.4 B). Although the... 

Thr-1, Asp-56, Arg-99 and Asn-104 in the p7 subunit, and Tyr-88 of the pi subunit, are conserved between the bovine and yeast proteasomes. The three-dimensional locations of the functional groups of these residues are also similar in the two species, except for Thr-1. Structural comparison of the two structures suggested that the N-terminal chain in the yeast subunit can change its conformation to match that of the novel Ntnhydrolase-active site in the bovine proteasome. However, SNAAP activity has not been reported for the yeast enzyme. 

The types of nitrogen-containing compounds that are most frequently involved in reductive biotransformation are those containing nitro, azo, and N-oxide functional groups. Similar enzymes are involved that are generally located in the endoplasmic reticulum or cytosol of the liver or in the intestinal microflora. Complete reduction of a nitro compound to the primary amine involves a six-electron transfer and proceeds through nitroso and hydroxylamine intermediates [Eq. (16)]. 

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