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The Inflammatory Response: A Bridge Between The Constitutive and Inducible Systems
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
A third pathway is activated by binding of marinóse binding lectin (MBL) to mannose residues on micro-organisms. MBL is produced by liver cells as a rapid response to inflammation. Binding of MBL to micro-organisms allows subsequent binding and activation of a serum serine protease that can cleave and activate complement factor 4. This facilitates the activation of downstream components of the complement cascade. The alternative and MBL-activated pathways of complement activation are important constituents of innate immunity.
Antibiotics: The Need for Innovation
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The transpeptidase enzyme is classified as a serine protease; where a serine residue in the active site is involved in hydrolysis of peptide bonds. The serine acts as a nucleophile to split the two D-alanine units on a peptide chain. The terminal alanine departs, while the peptide remains in the active site. Another peptide chain enters the active site and a peptide bond is formed between D-alanine and the terminal glycine of the other chain. It is presumed that the penicillin conformation mimics the transition state conformation of the D-Ala-D-Ala moiety during the cross-linking reaction and the transpeptidase enzyme mistakenly binds it to the active site. The serine residue acts as a nucleophile and opens the β-lactam ring, but because the molecule is cyclic, it is not split in two as the peptide would be. Consequently, nothing leaves the active site, which is blocked and access to the second peptide chain is prevented. As a result, cross-linking in the bacterial cell wall is inhibited, making it fragile and lysis occurs.
Ultratrace Minerals
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Borates and other organoboron compounds inhibit two major classes of enzymes — oxidoreductases and serine proteases.1001,1006 In oxidoreductases, boron competes with pyridine or flavin nucleotide cofactors (NADH, NADPH, and FAD).1001 Examples include alcohol dehydrogenase, xanthine oxidase, glyceraldehyde-3-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and cytochrome b5 reductase.1002 Thrombin, chymotrypsin, and subtilisin are known to be inhibited by borate.1001 Other serine proteases are important mediators of inflammation and resulting tissue damage.150 Thus, boron may possess potential antiinflammatory actions by inhibition of enzymes used to promote inflammation, tissue degradation, and leukocyte respiratory burst (free radical formation). However, before any conclusions about the antiinflammatory nature of boron can be made, concentrations for in vitro effects must be matched to localized in vivo levels. The possible antiinflammatory effects of boron compounds deserve further attention.
Investigational drugs in clinical trials for macular degeneration
Published in Expert Opinion on Investigational Drugs, 2022
Michael J Tolentino, Andrew J Tolentino
The complement pathway is a complex interplay of serine proteases that requires activation, amplification and lysis. This pathway involves multiple enzymatic processes. The most critical process is the formation of c3 convertase C3bBb. The alternative pathway is regulated by complement factor H which binds to c3b in order to displace Bb and degrade c3 convertase. This critical step is the ideal target for complement pathway inhibition. Complement factor D is important in producing the Bb portion of C3 convertase. While critical and rate limiting, inhibiting mature factor D may not be enough to reduce factor D adequately. Factor D is produced as a pro-enzyme and requires cleavage of 6-amino acid peptide for maturation. This cleavage is under the control of mannose-binding lectin–associated serine protease-3 which is involved in the lectin complement pathway. To inhibit factor D effectively in the majority of patients, inhibition of both factor D and its proenzyme may be necessary. The other possibility is that Factor D may not play such a critical role in the alternative pathway as thought, and may be more critical for the lectin pathway [91].
Trends in nanoformulations for atopic dermatitis treatment
Published in Expert Opinion on Drug Delivery, 2020
Estefânia Vangelie Ramos Campos, Patrícia Luiza De Freitas Proença, Lorena Doretto-Silva, Vinicius Andrade-Oliveira, Leonardo Fernandes Fraceto, Daniele Ribeiro de Araujo
The cellular composition of the skin is organized in three large layers: the epidermis (in contact with the external environmental), dermis, and hypodermis. Each contains immune cells [4]. Any dysregulation in these layers, e.g., external stimuli, can cause inflammation and compromise tissue function. AD patients have an unbalanced immunity, weakened skin barrier performance, and are more susceptible to Staphylococcus aureus infection [5]. The stratum corneum (SC) provides a physical and functional barrier to the body and is affected in AD patients. Both lesional and non-lesional skin shows an imbalanced on SC homeostasis leading to increased trans-epidermal water loss, susceptibility to pathogens, and enhanced penetration of exogenous allergens [6,7]. Impaired SC results from the alteration in the morpho-functional features of corneocytes, pH increase, and intracellular lipid matrix are due to three main factors: (a) compromised lipid process; (b) enhanced serine protease activity; and (c) defects in the production and/or function of filaggrin protein [8–10].
Antiplatelet properties of snake venoms: a mini review
Published in Toxin Reviews, 2020
Rogayyeh Rashidi, Mahmoud Gorji Valokola, Seyedeh Zohreh Kamrani Rad, Leila Etemad, Ali Roohbakhsh
Snake venom serine proteases (SVSPs, 20–100 kDa) have been extracted mainly from venoms of Viperidae, Elapidae, Viperidae, Hydrophidae, and Colubridae families (Vaiyapuri et al. 2011). They have a conserved domain consisting of three amino acids including histidine, serine, and aspartic acid. All of these amino acids participate in the catalytic activity of the enzymes (Fatima and Fatah 2014). Most of the serine proteases target platelets, coagulation process, and the fibrinolytic system. A few venom serine proteases specifically activate coagulation factor V, protein C, plasminogen, and platelets (Serrano and Maroun 2005). These enzymes have been named as snake venom thrombin-like enzymes (SVTLEs) (Castro et al. 2004). The main recognized target for SVSPs is the coagulation cascade. They are potent platelet aggregating biomolecules and act as exogenous factors of the plasma (Kini 2005, Serrano 2013, Fatima and Fatah 2014). FXa, a trypsin-like serine protease plays a key role in both internal and external coagulation pathways. Therefore, it has the main role in the production of thrombin, which leads to clot formation and wound closure (Jiang et al. 2014, Chen et al. 2015). Some serine proteases present thrombin-like properties and induce abnormal fibrin clots (Figure 2). However, there are snake venoms such as batroxase with both fibrinolytic and fibrinogenolytic activity (Cintra et al. 2012). Some others, such as AHP-Ka, have kininogenase (kallikrein-like,) properties that increase bradykinin and exhibit hypotensive effects (Zhang et al. 2012).