Serine residues mammalian

The catalytic mechanism of the subtilisins is the same as that of the digestive enzymes trypsin and chymotrypsin as well as that of enzymes in the blood clotting cascade, reproduction and other mammalian enzymes. The enzymes are known as serine proteases due to the serine residue which is crucial for catalysis (Kraut, 1977 and Polgar, 1987)... 

It is important to know that the inhibition of acetylcholinesterase by OPs is through an attack on the relatively positive phosphorus atom by the hydroxyl group of a serine residue at the enzyme s site of action. Electron withdrawing substitutions within the OP tend to make the phosphorus more positive and, therefore, more reactive. Unfortunately, this type of substitution also makes the compound less stable hydrolytically. The discovery and development of OP insecticides has always been a balance between activity against the enzyme of the insect, selectivity in comparison with mammalian systems and stability within the insect. The binding of OPs to acetylcholinesterase is often irreversible. Typical OP insecticides are shown in Figure 3.3. 

The mammalian serine proteases have a common tertiary structure as well as a common function. The enzymes are so called because they have a uniquely reactive serine residue that reacts irreversibly with organophosphates such as diisopropyl fluorophosphate. The major pancreatic enzymes—trypsin, chymotrypsin, and elastase—are kinetically very similar, catalyzing the hydrolysis of peptides... 

The amino acid sequence around the serine that is phosphorylated in the presence of inorganic phosphate at low pH can be seen in Table III (55-57). The sequence of Schwartz et al. (55) accounted for 56% of the peptides that contained 32P (20% or more of the peptides were excluded as extreme fractions when the peaks were pooled). The sequence, as far as it is known, is the same for alkaline phosphatase from a mammalian source (58). It is interesting to note, as pointed out by Boyer and others (59-64), that many hydrolytic enzymes with a serine residue at their active site have the same general sequence, i.e., Asp (Glu)-Ser-Ala (Gly). 

The serine proteases are a large family of proteolytic ( enzymes that use the reaction mechanism for nucleophilic catalysis outlined in equations (3) and (4), with a serine residue as the reactive nucleophile. The best known members of the family are three closely related digestive enzymes trypsin, chymotrypsin, and elastase. These enzymes are synthesized in the mammalian pancreas as inactive precursors termed zymogens. They are secreted into the small intestine, where they are activated by proteolytic cleavage in a manner discussed in chapter 9. 

Topography of glycophorin in the mammalian erythrocyte membrane. Carbohydrate residues (small blue hexagons) are attached to the hydroxyl groups of threonine and serine residues in the N-terminal domain of the protein. The N-terminus and all of the carbohydrates are outside the cell the C-terminal domain of the protein is inside. The hydrophobic, membrane-spanning domain is flanked by charged amino acid residues that may interact electrostatically with the polar head-groups of the phospholipids. 

The CBS prediction server also provides services for predicting O-glycosylation sites (NetGly) in mammalian proteins (http //www.cbs.dtu.dk/services/NetQGly-2.0/) and phosphorylation sites (NetPhos) in eukaryotic proteins (http //www.cbs.dtu.dk/ services/NetPhos/). Paste the query sequence and click the Submit Sequence button to receive the predicted results. NetOGly returns tables of potential versus threshold assignments for threonine and serine residues as well as a plot of O-glycosylation potential versus sequence position. NetPhos returns tables of context (nanopeptides, [S,T,Y] + 4 residues) and scores for serine/threonine/tyrosine predictions. 

The inner nuclear membrane of the nucleus in mammalian cells is supported by a network of intermediate filaments called the nuclear lamina which is comprised of lamins. In late prophase of mitosis, the nuclear membrane fragments into vesicles triggered largely by phosphorylation of the lamins at various serine residues. This serves to disassemble the nuclear lamina. At the completion of mitosis, dephosphorylation of the lamins allows the vesicles in each of the new daughter cells to reform nuclear membranes surrounding the chromosomes. 

The allyl group played a key role in a synthesis of a phosphorylated and glycosylated peptide fragment of mammalian RNS polymerase II.48 The allyl group was selected for the protection of both the phosphate and amino group of the terminal serine of the hexapeptide 26 1 [Scheme 7.26], because its reductive cleavage with butylammonium formate and Pd(0) could be accomplished without elimination of the phosphate or N-acetylglucosamine units attached to the three serine residues. 

Serine Racemase (EC 5.1.1.16] Serine racemases have been discovered in both bacteria and eukaryotes (for a review see [60, 62). In the latter organisms, serine racemase catalyzing the conversion of L-Ser to D-Ser was at first discovered in the silkworm Bombyx mori it is a PLP-dependent racemase which is also active on L-Ala (-6% of the activity on L-Ser). A serine racemase was also purified from rat brain (and a serine racemase cDNA was cloned from mouse brain). Mammalian serine racemase shows sequence simUarily with L-threonine dehydratase from various sources all the active site residues of the latter enzyme are also conserved in mouse serine racemase. Mammalian serine racemase is a member of the fold-type II group of PLP enzymes (similarly to L-threonine dehydratase, D-serine dehydratase, and so on) and distinct from alanine racemase, which belongs to the fold-type III group. Mouse serine racemase shows a low kinetic efficiency the Km values for L- and D-Ser are -10 and 60 mM, respectively and the V ax values with L- and D-Ser are 0.08 and 0.37 units/mg protein (less than 0.1% of those of alanine racemase on L- and D-Ala, see above). 

The strategy used by the cysteine proteases is most similar to that used by the chymotrypsin family. In these enzymes, a cysteine residue, activated by a histidine residue, plays the role of the nucleophile that attacks the peptide bond (see Figure 9.18). in a manner quite analogous to that of the serine residue in serine proteases. An ideal example of these proteins is papain, an enzyme purified from the fruit of the papaya. Mammalian proteases homologous to papain have been discovered, most notably the cathepsins, proteins having a role in the immune and other systems. The cysteine-based active site arose independently at least twice in the course of evolution the caspases, enzymes that play a major role in apoptosis (Section 2.4.3). have active sites similar to that of papain, but their overall structures are unrelated. 

We next examine the coordinated functioning of the mammalian fatty acid synthase. Fatty acid synthesis begins with the transfer of the acetyl group of acetyl CoA first to a serine residue in the active site of acetyl transferase and then to the sulfur atom of a cysteine residue in the active site of the condensing enzyme on one chain of the dimeric enzyme. Similarly, the malonyl group is transferred from malonyl CoA first to a serine residue in the active site of malonyl transferase and then to the sulfur atom of the phosphopantetheinyl group of the acyl carrier protein on the other chain in the dimer. Domain 1 of each chain of this dimer interacts with domains 2 and 3 of the other chain. Thus, each of the two functional units of the synthase consists of domains formed by different chains. Indeed, the arenas of catalytic action are... 

D-Xylose is unusual as a structural component in mammalian cells. It is only present as the linker between protein and carbohydrate in proteoglycans, a class of extracellular macromolecules composed of glycosaminoglycan (GAG) chains attached to a core protein. Biosynthesis of GAG chains starts with the formation of a glycosidic bond between a serine residue of the protein and the unique o-xylose of the GAG chain. Then a specific linker tetrasaccharide is synthesized and is used as the acceptor for the elongation of GAG chains (Fig. 8). 

Because the bacterial enzymes are much more readily soluble than the mammalian, the steps of fatty acid synthesis have been elucidated in E. coli. The multiple-enzyme complex has been resolved into at least 7 protein components, 6 of which have specific enzyme activities. The other is referred to as the acyl carrier protein. The bacterial carrier protein (mol wt approximately 16,000) is rich in acidic residues and contains a 4 -phosphopantothenic prosthetic group, which, as we shall see, plays a key role in the binding of the acyl group. The prosthetic group is bound to a serine residue of the carrier protein. The carrier protein acts as an acceptor of the acetyl group attached to the SH group of CoA in a reaction catalyzed by an enzyme, acetyl-CoA-ACP transacylase ... 

---