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Enzymatic Degradation of Bradykinin
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Randal A. Skidgel, Ervin G. Erdös
At present, other potential functions of carboxypeptidase D are still unknown, but hypothetically it could be involved in peptide and protein processing in the constitutive secretory pathway, analogous to the participation of carboxypeptidase E in prohormone processing in the regulated secretory pathway. Whether mammalian carboxypeptidase D can also act as a hepatitis B virus-binding protein is unknown, but this might be a fruitful area for further investigation.
PEPTIDES
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
Hook and La Gamma (1987) demonstrated that carboxypeptidase H can be inhibited by its peptide products at concentrations similar to those seen within chromaffin vesicles. Inhibition by amidated peptide products (vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone) shows that the final products of the precursor processing pathway can regulate carboxypeptidase H. The enzyme was inhibited by proenkephalin-derived peptides but at higher concentrations. Hook and La Gamma (1987) suggested that product inhibition of carboxypeptidase H and perhaps other processing enzymes may serve to limit the peptide concentration within chromaffin vesicles.
Pituitary Melanotropin Biosynthesis
Published in Mac E. Hadley, The Melanotropic Peptides, 1988
The proteolytic cleavage of ACTH(1-39) in the pars intermedia involves a complex series of steps that terminate with the amidation of ACTH(1-14).65 In the sequence of ACTH(1- 39) the proteolytic recognition site is a block of basic amino acids at position 15-18 (Figure 3). Apparently as a result of steric hinderance, the proline residue at position 19 protects the C-terminal of Arg18 from proteolytic attack. Thus, CLIP, the C-terminal portion of ACTH(1-39), has Arg18 as the N-terminal residue. Because of this interaction, the proteolytic processing of ACTH(1-39) may occur at either residues 15, 16, or 17. Processing at these sites could result in the generation of several potential intermediates including: ACTH(1-17), ACTH(1-16), or ACTH(1-15). Figure 3 presents a potential mechanism to explain these cleavage events. In this model an as yet unidentified “proteolytic processing enzyme” would cleave at the C-terminal of residue 17 to generate ACTH(1-17). Carboxypeptidase H, an enzyme specific for substrates that terminate with a basic amino acid,66 would sequentially remove Arg17, Lys16, and Lys15 to generate the glycine-extended intermediate ACTH(1-14). Carboxypeptidase H is present in pars intermedia secretory granules.72 This model represents just one possible mechanism for generating ACTH(1-14). Other mechanisms which involve ACTH(1-16) or ACTH(1-15) as the initial proteolytic cleavage product are equally possible.
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
Carboxypeptidases (EC 3.4.16–3.4.18) are peptidases that cleave a peptide bond at the carboxy-terminal (C-terminal) end of a peptide or protein. Carboxypeptidases are named with a combination of one letter and one number following the word carboxypeptidase at the beginning. There are at least 17 carboxypeptidases, belonging to two major groups. One uses serine as an active site residue named as serine carboxypeptidases, and the other uses zinc at the active site, known as metallocarboxypeptidases, which are further separated into two subgroups based on amino acid sequence similarities [66]. Among the carboxypeptidases, some of them have low tissue specificity with expression in many tissues and are secreted into bodily fluids with a low concentration, such as carboxypeptidases D and X2. Some are in specific tissues without leaking into bodily fluids or with a low concentration in bodily fluids, such as carboxypeptidase A4 in the esophagus and skin, carboxypeptidase A6 in the intestine, prostate, and retina, carboxypeptidase E in the brain, carboxypeptidase M in the adipose, carboxypeptidase O in the intestine, X1 in the placenta, and carboxypeptidase Z in the ovary. And others are produced in specific tissues and then secreted into either small intestinal fluid or blood. Carboxypeptidases A1, A2, and B1 are produced in the pancreas and activated in the duodenum. All three proteins are zinc-containing metallopeptidases [67]. Compared to the high abundance of trypsin, chymotrypsin and elastase in the small intestine, carboxypeptidases such as A1, A2, and B1, have a much lower concentration.
Exploring neuropeptide signalling through proteomics and peptidomics
Published in Expert Review of Proteomics, 2019
Samantha Louise Edwards, Lucas Mergan, Bhavesh Parmar, Bram Cockx, Wouter De Haes, Liesbet Temmerman, Liliane Schoofs
One of the earliest applications of proteomics in the context of neuropeptides was to study the first steps of neuropeptide signaling: neuropeptide synthesis and processing. In a first study, dense core vesicles (DCV) from bovine chromaffin cells were lysed, soluble and membrane fractions were subjected to one-dimensional SDS-PAGE, and tryptic digests of gel slices were analyzed by LC-MS/MS. Proteins were identified from a variety of categories, including propeptides, proteases, and their regulators. As well as known components of these processing pathways, such as prohormone convertases 1 (PC1/3) and 2 (PC2) and carboxypeptidase E (CPE), novel elements were also discovered, such as cathepsins B and D, which at the time were known primarily as lysosomal proteins [44,45]. A similar approach was later used upon DCV of human pheochromocytoma, a tumor of the adrenal medulla. Normalized spectral abundance factor analysis was applied for relative quantification of over 300 of the identified proteins. PC1/3, PC2 and CPE were the most abundant propeptide-cleaving proteases, and their regulators proSAAS and 7B2 were also present [46,47]. Studies such as these contribute to a more complete picture of neuropeptide production in DCV, the primary stage of neuropeptide signaling.