scholarly journals Comparative properties of three functionally different but structurally related serpin variants from horse plasma

1991 ◽  
Vol 274 (2) ◽  
pp. 465-471 ◽  
Author(s):  
J Potempa ◽  
J K Wunderlich ◽  
J Travis
Keyword(s):  
Peptide Bond ◽  
High Rate ◽  
Reactive Site ◽  
Association Rate ◽  
Elastase Inhibitor ◽  
Oxidative Inactivation ◽  
Methionine Residue ◽  
Horse Plasma ◽  
Oxidation Resistant ◽  
Association Rate Constants

Three structurally related but functionally different serpins from horse plasma were isolated and characterized. In spite of their identical N-terminal sequences, which show some similarity to that of human alpha 1-proteinase inhibitor, the reactive-centre loops of each of these proteins show extensive variation. Only inhibitor I, with a P1 methionine residue, resembles human alpha 1-PI with regard to (a) similarity of amino acid sequence in the vicinity of the reactive-site peptide bond, (b) broad inhibitory specificity, (c) sensitivity to oxidative inactivation and (d) high rate of reactivity with neutrophil elastase(s). Inhibitor II, with a P1 arginine residue, is an exclusive trypsin inhibitor, and inhibitor III is an oxidation-resistant slow-reacting elastase inhibitor with a P1 alanine residue. Comparison of association rate constants for the inhibition of horse neutrophil elastases by the three inhibitors indicates that only inhibitor I is likely to be physiologically important in the regulation of these enzymes.

scholarly journals Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence

2011 ◽  
Vol 392 (5) ◽  
Author(s):  
Tomasz Kantyka ◽  
Karolina Plaza ◽  
Joanna Koziel ◽  
Danuta Florczyk ◽  
Hennig R. Stennicke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Serine Proteases ◽  
Peptide Bond ◽  
Cysteine Proteases ◽  
Reactive Site ◽  
Association Rate ◽  
High Association ◽  
Endogenous Protease ◽  
Covalent Complex

AbstractBacterial proteases are considered virulence factors and it is presumed that by abrogating their activity, host endogenous protease inhibitors play a role in host defense against invading pathogens. Here we present data showing thatStaphylococcus aureuscysteine proteases (staphopains) are efficiently inhibited by Squamous Cell Carcinoma Antigen 1 (SCCA1), an epithelial-derived serpin. The high association rate constant (kass) for inhibitory complex formation (1.9×104m/s and 5.8×104 m/s for staphopain A and staphopain B interaction with SCCA1, respectively), strongly suggests that SCCA1 can regulate staphopain activityin vivoat epithelial surfaces infected/colonized byS. aureus. The mechanism of staphopain inhibition by SCCA1 is apparently the same for serpin interaction with target serine proteases whereby the formation of a covalent complex result in cleavage of the inhibitory reactive site peptide bond and associated release of the C-terminal serpin fragment. Interestingly, the SCCA1 reactive site closely resembles a motif in the reactive site loop of nativeS. aureus-derived inhibitors of the staphopains (staphostatins). Given thatS. aureusis a major pathogen of epithelial surfaces, we suggest that SCCA1 functions to temper the virulence of this bacterium by inhibiting the staphopains.

scholarly journals The primary elastase inhibitor (elastasin) and trypsin inhibitor (contrapsin) in the goat are serpins related to human α1-anti-chymotrypsin

1995 ◽  
Vol 306 (1) ◽  
pp. 191-197 ◽  
Author(s):  
J Potempa ◽  
J J Enghild ◽  
J Travis
Keyword(s):  
Trypsin Inhibitor ◽  
Neutrophil Elastase ◽  
Proteinase Inhibitors ◽  
Specific Inhibitor ◽  
Serine Proteinase ◽  
Peptide Bond ◽  
Reactive Site ◽  
Elastase Inhibitor ◽  
Efficient Inhibitor ◽  
Inhibitory Specificity

Two primary serine proteinase inhibitors in goat plasma have been isolated and characterized. The N-terminal sequence analysis of the purified proteins revealed that they are closely related to each other and are highly homologous to human alpha 1-anti-chymotrypsin rather than alpha 1-proteinase inhibitor. However, despite structural similarities the inhibitory specificity of the goat inhibitors differed from each other and from that of anti-chymotrypsin. In contrast with human anti-chymotrypsin, one of the goat inhibitors was shown to be a strong and specific inhibitor of trypsin (k(ass.) = 1.9 x 10(6) M-1.s-1), whereas the other was an efficient inhibitor of neutrophil elastase (k(ass.) = 1.5 x 10(6) M-1.S-1). Differences in the inhibitory specificity of each protein could readily be attributed to the amino acid sequence within the reactive site region. The trypsin inhibitor with an assumed arginine residue at the P1 position of the reactive-site peptide bond is referred to as ‘contrapsin’, and indicates that the occurrence of contrapsins is not restricted to rodents. In contrast, the inhibitory specificity, resistance to oxidative and proteolytic inactivation and the presence of a P1 leucine residue in the elastase inhibitor is unique among inhibitory serpins that have been characterized to date. Because this serpin is apparently the major elastase inhibitor in goat plasma, it is likely to be involved in the control of goat neutrophil elastase. Therefore, we suggest the name ‘elastasin’, and extend it to any other anti-chymotrypsin related serpins possessing neutrophil-elastase- inhibitory activity.

scholarly journals Effect of heparin on the glia-derived-nexin-thrombin interaction

1989 ◽  
Vol 257 (1) ◽  
pp. 191-196 ◽  
Author(s):  
A Wallace ◽  
G Rovelli ◽  
J Hofsteenge ◽  
S R Stone
Keyword(s):  
Rate Constants ◽  
Antithrombin Iii ◽  
Kinetic Properties ◽  
Association Rate ◽  
High Affinity ◽  
Diffusion Controlled ◽  
Different Types ◽  
Human Thrombin ◽  
Alpha Beta ◽  
Association Rate Constants

In order to determine the specificity of the interaction between thrombin and glia-derived nexin (GdN), the inactivation of proteolytically modified human thrombin species by GdN has been studied. The second-order rate constants for the inactivation of alpha-, beta T-, gamma T- and epsilon-thrombin by GdN were 1.41, 0.63, 0.33 and 1.91 microM-1.s-1 respectively. The kinetic properties of gdN were also investigated in the presence of different types of heparin, fractionated according to antithrombin III-binding affinity. Association rate constants of both gdN and antithrombin III with alpha-thrombin were obtained using unfractionated, low- and high-affinity heparin types. The different heparin types gave optimal rates of inhibition at similar heparin concentrations for both inhibitors. At optimal heparin concentrations, the rate of inactivation of alpha-thrombin by GdN was 0.5-1.2 nM-1.s-1, which suggests that, under these conditions, the interaction is diffusion-controlled.

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