Serine proteinase inhibitor

Konarev AV, Anisimova IN, Gavrilova VA, et al. Serine proteinase inhibitors in the Compositae distribution, polymorphism and properties. Phytochemistry 2002 59 279-291. 

Brazzein is another small sweet-tasting protein whose solution structure has been recently solved by NMR. Brazzein tastes 2000 times sweeter than sucrose on a weight basis and is exceptionally thermostable. As indicated by NMR, the structure of this 54 residue, single-chain polypeptide does not change between 32 and 82 °C and retains its sweetness after incubation at 98 °C for two hours.Brazzein contains one a-helix and three strands of antiparallel jd-sheet stabilized by four intramolecular disulphide bonds. It has been proposed that the disulphide bonds could be responsible for the thermostability of brazzein by forming a compact structure at the tertiary level.The structure of brazzein does not resemble that of the other two sweet proteins with known structures, monellin and thaumatin, whereas sequence alignment and structural prediction indicate that brazzein shares the fold of a newly identified family of serine proteinase inhibitors. 

A compound that reduces the activity of an enzyme is known as an inhibitor. Inhibitors are usually small molecules but some are peptides or proteins. For example, there are a number of proteolytic enzymes in the blood that have serine in their active site. If the activities of these enzymes are too high, they can cause problems. Consequently, inhibitor proteins, known as serine proteinase inhibitors (serpins), are present in blood indeed, about 10% of all the plasma proteins are serpins (Box 3.4). 

SERINE DEHYDRATASE SERINE DEHYDRATASE SERINE DEHYDROGENASE Serine esterase inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE SERINE HYDROXYMETHYLTRANSFERASE SERINE PALMITOYLTRANSFERASE Serine protease inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE Serine proteinase inhibitor,... 

Serine Proteinase Inhibitor I Serine Proteinase Inhibitor II Cysteine Proteinase Inhibitor Aspartic Proteinase Inhibitor Polyphenol Oxidase... 

Nilges, M., Gronenborn, A. M., Brunger, A. T. and Clore, G M. (1988). Determination of three-dimensional structures of proteins by simulated annealing with interproton distance restraints Application to crambin, potato carboxypeptidase inhibitor and barley serine proteinase inhibitor 2. Protein Eng. 2, 27-38. 

Christensson A, Laurell CB, Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem. 1990 194 755-763. 

Doring, G. 1999. Serine proteinase inhibitor therapy in a(l)-antitrypsin inhibitor deficiency and cystic fibrosis. Pediatr. Pul-monoX. 28 363-375. 

Kalsheker N, Morley S, Morgan K Gene regulation of the serine proteinase inhibitors oq-antitrypsin and a, -an tich ymotrypsi n. Biochem Soc Trans 30 93-98,2002. 

Since aiAT represents the archetype for the serpin (serine-proteinase inhibitor) superfamily of proteins, it is possible that similar oxidative or proteolytic mechanisms may function in the inactivation of other serpins that are important in controlling the inflammatory cascade. Some serpins contain a readily oxidised reactive-centre methionine residue (e.g. plasminogen activator-inhibitor [108] and a2-antiplasmin [109]), whilst all serpins (including antithrombin III [110] and protease nexin I [111]) contain an exposed loop which is susceptible to cleavage by proteinases. 

In foliage, the concentrations of serine proteinase inhibitors are lower than that in seeds however, the induction of serine proteinase inhibitors has been reported in many plants including tobacco and tomato, and the inhibitors have been proven to function as a plant defense system.79-81 Leaf damage by the tobacco hornworm Manduca sexta was much bigger in tomato plant line deficient in proteinase inhibitor induction than in those that can induce proteinase inhibitor on herbivory.82... 

M. Nilges, A. M. Gronenborn, A. T. Brunger, and G. M. Clore, Protein Engin., 2,27 (1988). Determination of Three-Dimensional Structures of Proteins by Simulated Annealing with Interproton Distance Restraints. Application to Crambin, Potato Carboxypeptidase Inhibitor, and Barley Serine Proteinase Inhibitor 2. 

Interproton Distance Restraints. Application to Crambin, Potato Carboxypeptidase Inhibitor, and Barley Serine Proteinase Inhibitor 2. 

Most serine proteinase inhibitors interact with both regions of the active-site (1) the catalytic site and (2) the extended substrate-binding sites. This double interaction is especially prevalent for those inhibitors which are specific, that is, selective for one enzyme. The catalytic site is generally viewed as being composed of a catalytic triad, made up of Ser-195 [28], His-57 and Asp-102 (see Figure 2.1). At one time, it was widely accepted that catalysis was due to a charge-relay system established by these residues, but this hypothesis now seems unlikely [29]. 

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]. 

Local tissue inhibitors (TIMPs), a neutrophil-derived inhibitor and systemic inhibitors, such as a2-macroglobulin and the lower-molecular-weight prealbumin proteinase inhibitor, variably inhibit endogenous MMPs and neutrophil serine proteinases. Inhibitors are present in the mammalian cornea and in the tear film, where they maintain a dynamic equilibrium with endogenously or exogenously derived proteinases as part of the normal molecular homeostasis of the ocular surface. Where this equilibrium is deranged, either by local overexpression of enzyme or by reduction in inhibitory capacity, then keratolysis and ulceration are the probable results. 

Abnormal accumulation of elastase, a serine proteinase from human neutrophil, causes a number of acute and chronic inflammation diseases (Bernstein et al, 1994, cited in (1)). There is a demand for specific and potent exogenous inhibitors of proteinases, such as HNE, associated with these inflammatory processes (Stemlicht and Werb, 1999, cited in (1)). The serine proteinase inhibitor from tamarind seeds needs to be studies to determine whether it could have such application. Anti-inflammatory properties of tamarind fmit pulp were reported (7). 

Took, J.M.S.L.L Macedo, L.LP. Moura, G.E.D.D. Teixeira, F.M. Oliveira, A.S. Queiroz, A.F.S. Sales, M.P. A serine proteinase inhibitor isolated from Tamarindus indica seeds and its effects on the release of human neutrophil elastase. Life Sciences. 2005, 76,2881-2891. 

CHAPTER 36, FIGURE 7 A group of structurally similar protein inhibitors of the serine proteinases known as SERPINS (SERine Proteinase INhibitors). The structure shown is human antithrombin. The reference SERPIN, a j-proteinase inhibitor or a. -antitrypsin contains -30% a helix (9 helices) and 40% sheet (5 3 sheets). Other members of the SERPIN family contain both additional helices and p sheets. The reactive center loop of antithrombin, residues 378-396, contains the reactive site residues Arg and Ser . Upon reaction with the target proteinase or after cleavage by the target proteinase (a reaction that inactivates the inhibitor without inactivating the proteinase), the reactive center loop folds between the S3 and S5 sheets. 

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