Trypsinogen bonds

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

Proteolysis cleavage of peptide bonds to remodel proteins and activate them (ptoin-sulin, trypsinogen, prothrombinj... 

Protein digestion occurs in two stages endopeptidases catalyse the hydrolysis of peptide bonds within the protein molecule to form peptides, and the peptides are hydrolysed to form the amino acids by exopeptidases and dipeptidases. Enteropeptidase initiates pro-enzyme activation in the small intestine by catalysing the conversion of trypsinogen into trypsin. Trypsin is able to achieve further activation of trypsinogen, i.e. an autocatalytic process, and also activates chymotrypsinogen and pro-elastase, by the selective hydro-... 

This enzyme [EC 3.4.21.9], also known as enterokinase, activates trypsinogen by catalyzing the cleavage of Lys -lle bond in trypsinogen. 

Figure 12-12 Formation of the oxyanion hole following cleavage of trypsinogen between Lys 15 and He 16. (A) Stereoscopic view. (B) Schematic representation. The newly created terminal -NH3+ of He 16 forms a hydrogen-bonded ion pair with the carboxylate of Asp 194. This breaks the hydrogen bond between Asp 194 and His 40 in trypsinogen, inducing the peptide segment 192-194 to shift from an extended conformation to a helical form in which the NH groups of Gly 193 and Ser 195 form the oxyanion hole. Notice that the positions and interactions of Asp 102, His 57, and Ser 195, the catalytic triad, are very little changed. From Birktoft et al.270...

Some of the serine proteases are stored in the pancreas as inactive precursors that may be activated by proteolysis. Trypsinogen, for example, is converted to trypsin by the removal of the N-terminal hexapeptide on the cleavage of the bond between Lys-6 and Ile-7 by enterokinase. Chymotrypsinogen is activated by the tryptic cleavage of the bond between Arg-15 and He-16. (In this case, further proteolysis by the chymotrypsin that is released during the activation leads to the different forms of the enzyme—Figure 16.5.)... 

The inactive precursors are called trypsinogen, pepsinogen, chymotrypsino-gen, and procarboxypeptidase. These precursors are converted to the active enzymes by hydrolytic cleavage of a few specific peptide bonds under the influence of other enzymes (trypsin, for example, converts chymotrypsinogen to chymotrypsin). The digestive enzymes do not appear to self-destruct, probably because they are so constructed that it is sterically impossible to fit a part of one enzyme molecule into the active site of another. In this connection, it is significant that chymotrypsin attacks denatured proteins more rapidly than natural proteins with their compact structures of precisely folded chains. 

For trypsinogen activation, enteropeptidase (enterokinase, EC 3.4.21.9) [23] is a key enzyme for mammalian protein digestion. The selective cleavage site of trypsinogen by enteropeptidase initiates Lys6-Ile7 bond. Then trypsin (EC 3.4.21.4) activates other zymogens. Thus, the formation of trypsin by enteropeptidase is the master activation step. 

To probe the effects of the mutations on specificity at the Pi position, we used peptide substrates, Pro-Thr-Glu-Phe-Phe(4-N02)-Arg-Leu (PTEFF(4-N02)RL, peptide A ), Pro-Thr-Glu-Lys-Phe(4-N02)-Arg-Leu (PTEKF(4-N02)RL, peptide B ), and Ac-Ala-Ala-Lys-Phe(4-N02)-Ala-Ala-amide (Ac-AAKF(4-N02)AA-NH2, peptide C ). Peptide A was cleaved Phe-Phe(4-N02) bond, which represents pepsin-like activity, and peptide B and peptide C were cleaved at the Lys-Phe(4-N02) bond, which is equivalent to trypsinogen activation. No other bond in these peptides was hydrolyzed by any of the enzymes. From kinetic determination of... 

In conclusion, the double mutant pepsin T77D/G78(S)S79 was also able to activate bovine trypsinogen to trypsin by the selective cleavage of the Lys6-Ile7 bond of trypsinogen. Results of this study suggest that the structure of the active site flap contribute to the Si substrate specificity for basic amino acid residues in aspartic proteinases. 

Activation of trypsinogen by selectively cleavage of Lys6- -Ile bond at pH 4. Specific requirement for dibasic residues at P2 and PI Boc-Gln-Arg-Arg-j-MCA. 

Activation of trypsinogen by selectively cleavage of Lys6-J.-Ile bond. 

Many enzymes are synthesized as inactive zymogens and are activated only after secretion from their site of synthesis and storage. Activation is achieved by cleavage of one or more peptide bonds. A standard example is the secretion of trypsinogen and chymotrypsinogen from the pancreas into the gas-... 

In the duodenum, the pancreatic zymogens, trypsinogen, chymotrypsinogen, proelastase and procarboxypeptidase are converted into active enzymes by enteropeptidase and trypsin, as shown in Fig. 15-6. The activation of all the zymogens involves cleavage of peptide bonds and removal of peptides, enabling conformational changes and formation of a functional active site. 

The oxidation of trypsin and trypsinogen was carried out in aqueous 0.1 M acetate buffer solutions at room temperature. In this particular case and under these conditions no significant cleavage of peptide bonds next to tryptophan residues occurred. Careful analysis of hydrolyzates of NBS-oxidized trypsinogen and trypsin confirmed the selectivity of the oxidative modification of the protein, as Table XXIV shows. There is no significant loss of tyrosine, histidine, serine, threonine, or cystine, although all of these amino acids will react with NBS but considerably less rapidly than tryptophan. 

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