Peptides enzymes

Inhibitors as well as substrates bind in this crevice between the domains. From the numerous studies of different inhibitors bound to serine pro-teinases we have chosen as an illustration the binding of a small peptide inhibitor, Ac-Pro-Ala-Pro-Tyr-COOH to a bacterial chymotrypsin (Figure 11.9). The enzyme-peptide complex was formed by adding a large excess of the substrate Ac-Pro-Ala-Pro-Tyr-CO-NHz to crystals of the enzyme. The enzyme molecules within the crystals catalyze cleavage of the terminal amide group to produce the products Ac-Pro-Ala-Pro-Tyr-COOH and NHs. The ammonium ions diffuse away, but the peptide product remains bound as an inhibitor to the active site of the enzyme. 

The pigment, P(s), can, in principle, be any seawater-soluble particulate solid that is being considered for a potential use in a self-polishing antifouling paint. Salts, sugars, and proteins (enzymes, peptides, or hormones) are obvious examples. It should be noted that the pigment can also represent a seawater-... 

Fig. 19.7 Three possible orientations of the ligand HUB093 within the SI pocket of the enzyme peptide deformylase. Heavy atoms of the protein are coloured according to secondary chemical shift effects caused by the ring current...

Although this section deals mainly with the advantages of excised tissues with respect to nasal drug delivery studies, it is important to highlight some important attributes of nasal in situ perfusion model. Although this method does not provide data on systemic absorption, it enables study of the interactions of nasal mucosal enzymes, peptide substrates, and metabolic inhibitors and their implications for nasal drug absorption [13], It also enables the rate of nasal drug absorption to be determined. 

After the latter attaches, the AAs of the two adjacent complexes are linked by the action of the enzyme peptide synthetase (peptidyltransferase). Concurrently, AA and t-RNA of the left complex disengage. 

Hailing, P. J., Eichhorn, U., Kuhl, R, and Jakubke, H.-D. (1995). Thermodynamics of solid-to-solid conversion and application to enzymic peptide synthesis. Enzyme Microb. TechnoL, 17, 601-6. 

There are several other examples of enzyme peptide synthesis. The conversion of porcine insulin into a human insulin precursor, by replacing the B chain C-terminal with threonine, is still an important alternative to microbially produced human insulin. Peptides that are produced from ethyl esters of L-amino acids by BioEurope are used as ingredients of cosmetics. 

Tyrosinase is both an oxidase and a hydroxylase. Some other copper enzymes have only a hydroxylase function. One of the best understood of these is the peptidylglycine a-hydroxylating monoxygenase, which catalyzes the first step of the reaction of Eq. 10-11. The enzyme is a colorless two-copper protein but the copper atoms are 1.1 nm apart and do not form a binuclear center.570 Ascorbate is an essential cosubstrate, with two molecules being oxidized to the semidehydro-ascorbate radical as both coppers are reduced to Cu(I). A ternary complex of reduced enzyme, peptide, and 02 is formed and reacts to give the hydroxylated product.570 A related two-copper enzyme is dopamine (J-monooxygenase, which utilizes 02 and ascorbate to hydroxylate dopamine to noradrenaline (Chapter 25).571/572 These and other types of hydroxylases are compared in Chapter 18. 

How do antibiotics act Some, like penicillin, block specific enzymes. Peptide antibiotics often form complexes with metal ions (Fig. 8-22) and disrupt the control of ion permeability in bacterial membranes. Polyene antibiotics interfere with proton and ion transport in fungal membranes. Tetracyclines and many other antibiotics interfere directly with protein synthesis (Box 29-B). Others intercalate into DNA molecules (Fig. 5-23 Box 28-A). There is no single mode of action. The search for suitable antibiotics for human use consists in finding compounds highly toxic to infective organisms but with low toxicity to human cells. 

Many antibiotics, which inhibit protein synthesis, do not bind to ribosomes but block any of a variety of vital chemical processes needed for growth. Among them are pseudomonic acid, which inhibits isoleucyl-tRNA synthetase from many gram-positive bacteria.1111/VV Rapamycin, best known as an immunosuppressant (Box 9-F), inhibits phosphoinositide-3-kinase and also phosphorylation of the cap-binding protein 4G, a component of the eukaryotic initiation factor complex (Fig. 29-11 ).ww The bacterial enzyme peptide deformylase, which is absent from the human body, has been suggested as a target for design of synthetic antibiotics. 01... 

Antibody, enzyme, peptide, protein, or thiolated oligonucleotide to be conjugated to avidin. 

Heizmann, J., et al. 1996. Enzymatic cleavage of thymopoietin oligopeptides by pancreatic and intestinal brush-border enzymes. Peptides 17 1083. 

Peptide sequences related to those of snake venom peptides had already been used to define the structural requirements for peptide inhibitors of angiotensin-converting enzyme. Peptides are unstable in vivo and poorly ab-... 

New applications are envisaged in the near future, particularly in the emerging area of bio-separation such as purification of enzymes, peptides, antibiotics and natural extracts. Numerous companies offer SMB equipments for the pharmaceutical and the fine chemical industries [2,8]. This technology covers a broad range of production scales from the laboratory units, which use chromatographic... 

Besides thiol repair there also exists direct repair for one of the oxidation products of methionine, methionine sulfoxide. The enzyme peptide methionine sulfoxide reductase reduces the methionine sulfoxide formed in proteins due to oxidation and is therefore able to reconstitute the normal protein (Fig. 3). Besides methionine sulfoxide there exists a further oxidation product of methionine, methionine sulfone, which can not be repaired. The cycle of methionine oxidation and efficient methionine sulfoxide repair, and the early and easy oxidation of the methionine in proteins, led some authors to hypothesize that methionine acts as an intramolecular antioxidant for some proteins and so protects other amino acids from oxidation [12]. Besides the peptide methionine sulfoxide reductases, there also exists methionine reductases able to... 

In conclusion, among all known enzymes, peptide bond cis-trans isomerases exhibit a unique reaction profile with the potential of targeting a large number of rather similar reactive sites in a polypeptide chain, and a low degree of chemical differences that separates the reactant and product state of the enzyme reaction. 

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