Proposed counterion for Asp740 is Lys698 create salt-bridge Substrate Enzyme Mechanism Movie<unk>  belongs to a group of medications known as fibrinolytics, and complexes of<unk>  with human plasminogen can hydrolytically activate other unbound plasminogen by activating through bond cleavage to produce plasmin. There are three domains to<unk> , denoted α (residues 1–150), β (residues 151–287), and γ (residues 288–414). Each domain binds plasminogen, although none can activate plasminogen independently. Plasmin is produced in the blood to break down fibrin, the major constituent of blood thrombi, thereby dissolving clots once they have fulfilled their purpose of stopping bleeding. Extra production of plasmin caused by<unk>  breaks down unwanted blood clots, for example, in the lungs (pulmonary embolism). The usual activation of plasminogen is by proteolysis of the Arg561—Val562 bond. The amino group of Val562 then forms a salt-bridge with Asp740, which triggers a conformational change producing the active protease plasmin. When<unk>  is present, it binds to plasminogen to form a complex<unk> ·plasminogen) that converts substrate plasminogen to plasmin. Residues 1–59 of<unk>  regulate its capacity to induce an active site in bound plasminogen by a nonproteolytic mechanism and to activate substrate plasminogen in a fibrin-independent manner. This complex subsequently rearranges to an active complex although the Arg561–Val562 bond remains intact. Therefore, another residue must substitute for the free amino group of Val562 and provide a counterion for Asp740 in this active complex. Two candidates for this counterion have been suggested: Ile1 of<unk>  and Lys698 of plasminogen. Deletion of Ile1 of<unk>  markedly inhibits its capacity to induce an active site in plasminogen, which supports the hypothesis that establishment of a salt bridge between Ile1 of<unk>  and Asp740 of plasminogen is necessary for<unk>  to induce an active site in plasminogen by a nonproteolytic mechanism. In contrast with the Ile1 substitutions, the Lys698 mutations also decreased the dissociation constant of the<unk>  complex by 15 to 50 fold. These observations suggest that Lys698 is involved in formation of the initial<unk> ·plasminogen complex. Biology<unk>  is naturally produced by Streptococci spp. bacteria, which use this enzyme to break up blood clots so that they can spread from the initial site of infection. It can also activate fibrin. It is similar, both in function and in structure, to staphylokinase (Sak) found in Staphylococcus aureus. Staphylokinase is considered a virulence factor, although its presence after the establishment of infection actually decreases disease severity. Both enzymes are carried by phages.
Streptokinase
Thrombin
Serpin
Fibrinolysin
Prothrombinase
Angiozyme
Ocriplasmin
Coagulase