Proteinaceous inhibitors

The seeds and vegetative part of plants contain several sorts of inhibitors of insect, fungal, mammalian, and endogenous proteinases. These inhibitors may be involved in plant defense mechanisms against predators and participate in the development of the plant itself. Peptidic proteinase inhibitors are well studied in the families Fabaceae, Poaceae, Asteraceae, and Solanaceae (37). Non-proteinaceous inhibitors of serine... 

Merops (http //merops.sanger.ac.uk), database of peptidases and their proteinaceous inhibitors. Includes enzyme classification and nomenclature, external links to literature, and the structure of proteins of interest (if known). Enables one to find the gene coding for a given peptidase or to find the best enzyme to digest a chosen substrate. 

Structural mimicry of the substrate is also observed in the complex between PPA and the proteinaceous inhibitor tendamistat [173]. Again, the inhibitor extends into the catalytic site, but contacts only one of the catalytic residues, the glutamate residue. The sequence of three residues of the inhibitor, WRY (Trp-18 to Tyr-20) is positioned in the active site, with the arginine residue forming hydrogen bonds with the catalytic Glu-233. The WRY sequence and residues Thr-55, Gly-59 and Tyr-60 make hydrophobic contacts with the active site which are similar to those of acarbose and of a-All. 

Many serine proteinase inhibitors are active due to their ability to form a covalent link to Ser-195 of the enzyme. However, several proteinaceous compounds which are very potent serine proteinase inhibitors (K < 10" M) bind equa. y well to the parent enzyme and to the corresponding anhydroenzyme, in which the active-site serine has been replaced with dehydroalanine, proving that, with enough contact points, a covalent link to Ser-195 is not required for good activity [see section on proteinaceous inhibitors]. 

There are many high-molecular-weight, polypeptide, elastase inhibitors which have been isolated from animal or plant sources. Most of these, the non-human proteins, would probably induce an immunogenic response and are not suitable for clinical development. However, a subset of these inhibitors, predominantly human in origin, is being explored as a source for clinically-useful elastase inhibitors. Each of the human compounds is found in a specific location, which probably is its primary site for inhibitory action. The physical properties of many of these natural inhibitors have been reported (see Table 2.i)[45-51]. Due to their size and other physical properties, only intravenous or topical formulations of the proteinaceous inhibitors have been considered for clinical use. The pharmacological studies have included natural inhibitors, recombinant variants (i.e. peptides with identical sequences to the natural inhibitors but not necessarily the same glycosylation) and recombinant mutants (peptides with unnatural sequences) [52],... 

Theoretically, all of the proteinaceous inhibitors act by presenting a loop portion of their chains as an idealized, that is, pre-organized for optimal interactions, substrate for elastase. Conformational analysis of the inhibitor residues P P3 and P1-P3 for a series of proteinaceous, serine protease inhibitors showed that there is little difference between their free and/or complexed states [63]. In aj-PI, the loop contains as its elastase reactive center (see Table 2.2) a Met-Ser linkage. The importance of the P,-substituent in a PI for its enzyme specificity characteristics is exempli-... 

The enzyme inhibitor of monocytes (EIM), is a proteinaceous inhibitor of HLE which is found in human monocytes, neutrophils, and macrophages [72]. It was recently characterized and was shown to be made up of a single, 379 amino acid chain [48]. So far the detailed kinetic constants for EIM have not been reported nor is there any evidence that EIM is secreted [48]. The... 

Action patterns Adhesion domains Affinity and mechanism-based inhibitors Catalytic domains Classification schemes Hydrolases Lyases Mechanism of action Phosphorylases Proteinaceous inhibitors... 

The activity of the proteinaceous inhibitors isolated from animal cells is inversely correlated with the proliferation rate of their source. Only recently was such an inhibitor characterized as complex mixture of enzymes like phosphatases and kinases that act on the substrate CDP and on the effector ATP The assumption is justified that this class of substances merely interferes with the assay and does not define specific cellular inhibitors of ribonucleotide reductase. Nevertheless it must be realized that ribonucleotide reductase activity is well coordinated with cell proliferation and is strictly controlled within the cell cycle. Hence a regulatory role of inhibitors besides the control of gene expression and fine tuning by allosteric effectors is a priori conceivable. 

The majority of bacteriocins from lactic acid bacteria have been characterized according to the early definition of a proteinaceous inhibitor, estimation of their molecular mass, and determination of their inhibition spectrum [1,21]. Recent developments in the biochemical and molecular biological characterization of many of these compounds have elucidated their genetic organization, structures and mode of action. Despite their heterogeneity, bacteriocins produced by lactic acid bacteria were subdivided into three distinct classes based on these genetic and biochemical resemblances [28]. 

There are a number of natural and synthetic inhibitors known for CPA. Thus, a potent proteinaceous inhibitor was isolated from potato tuber that can inhibit not only CPA but also CPB with a Ki of 5 and 50 nM, respectively, but is inactive toward other common proteases, such as chymo-trypsin and trypsin. The mode of its inhibition was found... 

A proteinaceous inhibitor of rubber biosynthesis was purified from the C-serum of Hevea brasiliensis latex. The protein inhibited the incorporation of isopentenyl diphosphate into rubber. Purification was achieved by employing three column chromatography methods Sephadex G-150 gel filtration, DEAE-Cellulose ion exchange chromatography and Phenyl Sepharose CL-4B hydrophobic interaction chromatography. 21 refs. 

The methodology of Lubineau was also used by Tellier to graft acar-bose to Affigel-10 activated by NHS. The coupled gel was used to purify anti-Tendamistat polyclonal antibodies by cross reacting with acarbose. Since acorbose and Tendamistat are respectively carbohydrate and proteinaceous inhibitor to a amylase, the purified polyclonal antibodies were considered as good candidates for a amylase mimics. ... 

Watanabe T, Kondo N (1976) Isolation of a proteinaceous inhibitor of ethylene biosynthesis from marine algae. Agric Biol Chem 40 1877-1878 Webster PL (1967) Cell cycle kinetics in meristems Effects of colchicine and lAA. PhD Thesis, Case-Western Res Univ, Cleveland, Ohio Webster PL, Langenauer HD (1973) Experimental control of the activity of the quiescent centre in excised root tips of Zea mays. Planta 112 91-100 White KL, Hill AC, Bennett JH (1974) Synergistic inhibition of apparent photosynthesis rate of alfalfa by combinations of sulfur dioxide and nitrogen dioxide. Environ Sci Technol 8 574-576... 

Evidence has been reported for the presence of inhibitors of porcine pancreatic a-amylase in rye and wheat. The inhibitors were isolated by affinity chromatography on the agarose derivative-immobilized enzyme. The location in the seed, molecular properties, and biological role of proteinaceous inhibitors of a-amylase in wheat have been reviewed. Inhibition specificity of albumin inhibitors and structural features essential for interaction with inhibited amylases were also examined. The possible significance of these naturally occurring inhibitors in relation to their presence in foods in active form was described. 

Proteinaceous inhibitors of a-amylase in aqueous extracts of seeds of Triticum and related species have been characterized according to their molecular weights, electrophoretic mobilities, and specificities in inhibiting a-amylases from human saliva and Tenebrio molitor larvae. ... 

Satouchi, K. Matshushita, S. (1976) Proteinaceous inhibitors of lipase activity in germinating oilseeds, Agric. Biol. Chem. 888-897. 

Substances from plants that inhibit a-amylase activity have been reviewed. Wheat flour contains proteinaceous inhibitors of a-amylase, and the interactions of immobilized forms of the inhibitor with a-amylases were investigated. 

Kidney beans (Phaseolus vulgaris) contain a proteinaceous inhibitor of a-amylase named phaseolamin . After purification by heat treatment, ion-... 

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