Plasminogen activators and plasminogen activator inhibitors: biochemical aspects.
Although this chapter does not represent a historical review, it will be clear how the biochemistry of t-PA, u-PA, PAI-1 and PAI-2 has evolved and where we stand in 1994. While the functional activities of the proteins were recognized at least three to four decades ago, highly purified preparations became available around 1980. In the mid-eighties the cDNAs of the proteins were cloned, representing a major breakthrough in the biochemistry of the four proteins. Amino acid sequences were derived from the nucleotide sequences, homologies with other proteins were recognized and larger amounts of (recombinant) proteins became available for research. In addition, mutant proteins were prepared by recombinant DNA technology, enabling investigation of structure-function relationships. This report is mainly based on the latter studies. Detailed information about three-dimensional structures of the proteins and the mode of interaction with other macromolecules is still lacking. To obtain this information will be the goal for biochemists in the coming years.
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Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
D000595:Amino Acid Sequence; D000818:Animals; D005337:Fibrin / Q000494:pharmacology; D005342:Fibrinolysis; D006801:Humans; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017396:Plasminogen Activator Inhibitor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010960:Plasminogen Activators; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D015849:Plasminogen Inactivators; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator