cids from the N terminal sequence. This reduces pepsinogen's molecular weight of 43,000 by about 5,000 molecular weight (4:743-750). Ultimately, the gastric proteases consist of a single polypeptide chain containing three intramolecular disulfide bridges (3:57). Upon activation, this chain undergoes further conformational alteration (5:1-7). Pepsin is essentially a bilobal molecule. Its two domains are separated by a deep cleft lying perpendicular to the molecule's largest diameter. Zymogen activation is thought to expose active sites located within this cleft (3:61).
Bergman (1942) divided the proteolytic digestive enzymes into two classes. These consisted of the exo-peptidases and the endo-peptidases. Pepsin is an endo-peptidase. It cleaves peptide bonds within proteins and polypeptides (8:667). Moreover, although the enzyme acts on a wide variety of substrates, its proteolytic activity, does not take place indiscriminately. Pepsin has a distinct preference for the peptide bonds formed by such aromatic amino acids as tyrosine and phenylalanine (4:743-750). Polypeptide chains are typically cleaved wherever one of these residues occurs. This generally breaks proteins down into polypeptides containing about seven amino acids.
While several hypotheses have been proposed for pepsin catalysis, its precise mechanism remains unknown. For the most part though, active site aspartic acid and serine residues initially form an enzyme-substrate complex. The molecules' deep cleft is thought to
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