Elastase broad substrate specificity

Elastase is the name given to proteinases that possess the ability to hydrolyze mature cross-linked elastin [18]. Elastin is an insoluble structural protein responsible for the elastic properties of the lung, skin, and arteries and is quite resistant to most proteinases. Elastin is high in hydrophobic amino acid residues such as valine, alanine, glycine, and proline [19]. Insoluble elastin fibers contain cross-links usually between four lysine residues, which form a unique cyclic product, desmosine. The presence of soluble desmosine cross-links in plasma can be used as a measure of elastin breakdown. Of all the elastases in humans, neutrophil elastase has received the most attention over the years due to its broad substrate specificity and abundance within the cell. However, neutrophils and macrophages contain several proteinases (Table 1), which are capable of degrading elastin. 

In the recent studies, the enzyme shows that the overall polypeptide fold of chymotrypsin-like serine protease possesses essential SI specificity determinants characteristic of elastase using the multiple isomorphous replacement (MIR) method and refined to 2.3 A resolution Fig. (5). Structure-based inhibitor modeling demonstrated that EFEa s SI specificity pocket is preferable for elastase-specific small hydrophobic PI residues, while its accommodation of long and/or bulky PI residues is also feasible if enhanced binding of the substrate and induced fit of the SI pocket are achieved [Fig. (6) shows the active sites of serine protease]. EFEa is thereby endowed with relatively broad substrate specificity, including the dual fibrinolysis. This structure is the first report of an earthworm fibrinolytic enzyme component, a serine protease originated from annelid worm [17]. 

It occurred to have a broad primary specificity toward amino acids with hydrophobic side groups in synthetic ester and amide substrates. Pr2 exhibited rapid hydrolytic activity to casein and substrates containing Arg or Lys, while little or no activity was shown to cuticle, elastin, or substrates for chymotrypsin and elastase. The relation between Pr2 and trypsin was confirmed by the use of specific inhibitors. 

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