Literature summary for 3.4.21.68 extracted from

Gong, L.; Liu, M.; Zeng, T.; Shi, X.; Yuan, C.; Andreasen, P.A.; Huang, M.
Crystal structure of the Michaelis complex between tissue-type plasminogen activator and plasminogen activators inhibitor-1 (2015), J. Biol. Chem., 290, 25795-25804 .

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Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of the isolated serine protease domain (residues 276-527) wild-type and mutant S478A/C395A/N448Q of enzyme tPA in Pichia pastoris strain X-33. The Pichia pastoris Kex2p protease can cleave the secreted tPA-serine protease domain	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme in complex with plasminogen activator inhibitor-1, X-ray diffraction structure determination and analysis	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort	Homo sapiens
S478A/C395A/N448Q	site-directed mutagenesis in the serine protease domain	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
plasminogen activator inhibitor-1	PAI-1, endogenous PAI-1 inactivates the enzyme. Physiologically, PAI-1 inhibits plasminogen activators rapidly and irreversibly, PAI-1 inhibitory mechanism. Analysis of the overall structure of tPA-PAI-1 Michaelis complex, structure-function relationship, overview. The PAI-1 reactive center loop adopts a unique kinked conformation, and on the tPA side, the S2 and S1beta pockets open up to accommodate PAI-1. The deterined crystal structure provides detailed interactions between tPA 37- and 60-loops with PAI-1, overview Comparison to urokinase-type plasminogen activator (uPA, EC 3.4.21.73) structure with bound plasminogen activator inhibitor-1. As a result of the complex formation, an interface of 1202 A2 (solvent-inaccessible area) between PAI-1 and tPA-SPD is formed, which is higher than that of the uPA-SPDx02PAI-1 complex (1058 A2). Of the total area of PAI-1, 8% is involved in interacting with tPA, whereas for uPA, only 6.9% is at the interface. As a protease inhibitor, PAI-1 is very specific to tPA and uPA. Analysis of PAI-1 mutant 14-1B (N150H/K154T/Q319L/M354I)	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P00750	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	Pichia pastoris Kex2p protease can cleave the secreted tPA-serine protease domain	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and mutant isolated serine protease domain (residues 276-527)of enzyme tPA from Pichia pastoris strain X-33 by cation exchange chromatography and gel filtration	Homo sapiens

Synonyms

Synonyms	Comment	Organism
PLAT	-	Homo sapiens
Tissue-type plasminogen activator	-	Homo sapiens
tPA	-	Homo sapiens

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Release 2023.1 (January 2023)