Enzyme Specificity and substrate selectivity

Specificity is a property of the enzyme and describes how restrictive the enzyme is in its choice of substrate; a completely specific enzyme would have only one substrate.
The specificity of the serine proteases is usually not very high since they have similar active sites and act through the same proteolytic mechanism.
Consequently, a single serine protease may act on various substrates although at different rates. How the substrate fits the active site of the enzyme is of crucial importance to the outcome of the enzyme-substrate reaction. The bond to be cleaved must have a specific orientation relative to the amino acid side chains of the catalytic triad. The most important factor governing the fit of a substrate for an enzyme is the amino acid sequence around the bond to be cleaved. 

Trypsin cleaves amides and esters of the basic amino acids arginine and lysine. Thrombin has a similar preference, but is more specific for arginine than for lysine.
Selectivity is a property of the substrate and indicates the degree to which the substrate is bound to and cleaved by different enzymes. The best measure for selectivity is given by the ratio kcat/Km. Synthetic substrates are considerably smaller than the natural substrates and can usually be cleaved by more than one enzyme, i. e. synthetic substrates are not completely selective. The explanation for this is that large substrates such as fibrinogen not only interact with the active site but also with exterior domains of the enzyme. Such interactions allow substrates to discriminate between different serine proteases and fibrinogen thus becomes highly selective for thrombin.