Molecular Recognition and Chemical Modification of Biopolymers — Two Main Components of Affinity Modification
Dmitri G. Knorre, Valentin V. Vlassov in Affinity Modification of Biopolymers, 1989
However, the most striking feature of the enzymes is specificity. Thus, carboxypeptidase A catalyzes the hydrolysis of a C-terminal peptide bond and does not touch the internal bonds. Only the C-terminal l-amino acid is removed. The enzyme strongly prefers C-terminal residues with a hydrophobic side chain. All these features are due to the fact that the substrate should be recognized prior to being hydrolyzed. The recognition of a COO− group by an arginine residue of the enzyme Arg-145 and of the side chain by hydrohobic Ile-247 and Tyr-248 directs the C-terminal peptide bond to Zn2+ which operates as the electrophilic catalyst. In the case of C-terminal d-amino acid, recognition of COO− group and of the side chain by the same aminoacyl residues of the enzyme should direct to the catalytic center the hydrogen atom bound to assymetrical Cα instead of the peptide bond; no catalysis occurs. Thus, recognition is a foundation of the specificity of enzymes towards substrates including the stereospecificity.
The Renin-Angiotensin System
Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan in Pharmacological and Therapeutic Aspects of Hypertension, 2020
However, very high concentrations of angiotensin I may be handled in a different manner.251 Using near-physiological concentrations of angiotensin I injected into the pulmonary arteries of anesthetized rats, only angiotensin II and unaltered angiotensin I were found in the pulmonary venous effluent, indicating the action of converting enzyme. However, when higher doses of angiotensin I were administered, the converting enzyme appeared to become saturated, and a peptide resembling [des-Leu10]-angi-otensin I was found in the venous effluent in large quantities. The appearance of this peptide fragment indicates the action of a carboxypeptidase. The authors suggested that this dual enzyme system might allow protective inactivation of excessive amounts of angiotensin I reaching the lungs.
Enzymatic Degradation of Bradykinin
Sami I. Said in Proinflammatory and Antiinflammatory Peptides, 2020
Carboxypeptidase U is an unstable blood-borne carboxypeptidase that is activated during coagulation. In 1989, several groups reported that human serum has a much higher (about two- to threefold) arginine carboxypeptidase activity than plasma, and that the difference could not be explained by changes in carboxypeptidase N activity (Sheikh and Kaplan, 1989; Hendriks et al., 1989; Campbell and Okada, 1989). Further investigations showed that the enzyme is a unique carboxypeptidase (Campbell and Okada, 1989; Hendriks et al., 1990, 1992). Interestingly, Erdös and colleagues in 1964 (Erdös et al., 1964) noticed that serum had a higher carboxypeptidase activity than plasma, but the reason for the difference was not investigated further. In unrelated studies, the cDNA sequence of a plasminogen-binding protein had significant homology with pancreatic carboxypeptidase B (Eaton et al., 1991). Although many of the properties are quite similar to those of carboxypeptidase U, Eaton and coworkers named the one they isolated “plasma carboxypeptidase B.” Based on similarities in properties and partial sequence information, most investigators now believe they are identical (Wang et al., 1994, Shinohara et al., 1994). For the purposes of this review, “carboxypeptidase U” will be used to avoid the possible confusion that could arise from the name “plasma carboxypeptidase B,” employed for many years as a misnomer for carboxypeptidase N. The same protein was recently isolated and named TAFI, for “thrombin-activatable fibrinolysis inhibitor” (Bajzar et al., 1995).
Comprehensive characterisation of the heterogeneity of adalimumab via charge variant analysis hyphenated on-line to native high resolution Orbitrap mass spectrometry
Published in mAbs, 2019
Florian Füssl, Anne Trappe, Ken Cook, Kai Scheffler, Oliver Fitzgerald, Jonathan Bones
Using our native CVA-MS approach, we were able to obtain very high chromatographic resolution and successful identification of the majority of the 16 charge variants observed. Among them were proteoforms modified by different levels of C-terminal lysine truncation, deamidation, succinimide aspartic acid (Asp) formation, glycation and fragmentation. To investigate whether host cell proteins (HCPs) might be involved in the fragmentation of adalimumab, we performed an HCP analysis employing peptide mapping. Several HCPs were detected, among them the protease Cathepsin L, which could suggest the occurrence of the detected fragments to partly be due to enzymatic proteolysis. Carboxypeptidase B (CpB) digestion and peptide mapping experiments were performed as orthogonal methods to confirm the results obtained on the intact protein level.
Is individual genetic susceptibility a link between silica exposure and development or severity of silicosis? A systematic review
Published in Inhalation Toxicology, 2020
Kaio Cezar Rodrigues Salum, Marcos Cesar Santos Castro, Ângela Santos Ferreira Nani, Fabiana Barzotto Kohlrausch
Carboxypeptidase M (CPM) belongs to the family of the carboxypeptidases, which function is removing C-terminal amino acids from peptides and proteins and exert roles in physiological processes like inflammation. CPM has been suggested to play critical roles in inflammatory diseases (Deiteren et al. 2009), and a higher expression level of CPM may promote the progression of lung fibrosis (Chu et al. 2019). In fact, the relative expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls (Chu et al. 2019). Based on the hypothesis that the rs12812500 polymorphism is located on the promoter of the CPM gene and was associated with higher CPM expression, Chu et al. (2019) evaluated this polymorphism and observed the G allele was associated with an increased risk of silicosis in an additive genetic model controlled for confounders.
Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications
Published in Acta Cardiologica, 2021
Christiaan J. M. Vrints, Konstantin A. Krychtiuk, Emeline M. Van Craenenbroeck, Vincent F. Segers, Susanna Price, Hein Heidbuchel
ACE2, a homolog of the angiotensin-converting enzyme (ACE), was discovered 20 years ago [39,42]. This membrane-bound carboxypeptidase is universally present in the cardiovascular system as well as in the lung, intestine, and kidney. It hydrolyses angiotensin II (Ang II) to angiotensin 1–7 (Ang 1–7), which has vasodilator and cardioprotective effects through activation of the MAS receptor, coded by the MAS1 gene (mitochondrial assembly 1) [43,44] (Figure 3). By hydrolysing Ang II to Ang 1–7, ACE2 counterbalances the vasoconstriction induced by activation of the ACE-Ang II-angiotensin receptor 1 (AT1) axis of the RAS. In various diseases where the ACE-Ang II-AT1 axis is activated, ACE2 may mitigate the detrimental effects of Ang II [44]. As a consequence, impairment of the cardioprotective effects the ACE2-Ang [1-7]-MAS axis will accelerate the disease-promoting actions of an activated ACE-Ang II-AT1 axis. Furthermore, excess of Ang II in disease will further weaken the protective role of ACE2 by activating disintegrin and metalloprotease 17 (ADAM17), an enzyme that leads to shedding of the ectodomain of ACE2 from the cell membrane into the circulation [45,46]. A high concentration of this soluble ACE2 is a known marker of an unfavourable prognosis in patients with cardiovascular disease [47].
Related Knowledge Centers
- Aromaticity
- Carboxypeptidase
- Hydrolysis
- Pancreas
- Peptide Bond
- Mast Cell
- Exopeptidase
- Aliphatic Compound
- Side Chain
- Carboxypeptidase A2