Literature summary for 3.4.17.20 extracted from

Miah, M.F.; Boffa, M.B.
Functional analysis of mutant variants of thrombin-activatable fibrinolysis inhibitor resistant to activation by thrombin or plasmin (2009), J. Thromb. Haemost., 7, 665-672.

Search for more literature for 3.4.17.20

Activating Compound

Activating Compound	Comment	Organism	Structure
plasmin	overall catalytic efficiency for activation by plasmin is 1/5 of that for activation by thrombin in the presence of thrombomodulin	Homo sapiens
thrombin	poor activator of TAFI	Homo sapiens
thrombin-thrombomodulin	activation in the presence of thrombomodulin is considerably enhanced	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
-	Homo sapiens
recombinant TAFI is expressed in BHK cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A93V	mutant is comparably to wild-type activated by thrombin, mutant is slightly less activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.205, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000169, mutation shows no effect on the activation by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00043, Km (mM) (hippuryl-arginine, activated by plasmin): 0.00001, intrinsic stability of activated TAFI (half-life): 6.3 min	Homo sapiens
additional information	variant mutants are constructed and expressed mutant variants that have key substitutions in the amino acids surrounding the scissile Arg92-Ala93 bond. Variants are identified that show patterns of resistance to specific activators. The variants that are tested also showed antifibrinolytic potentials that can be rationalized in terms of which enzymes are capable of activating them	Homo sapiens
P91S	mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively	Homo sapiens
P91S	mutant is not activated by thrombin or by thrombin in the presence of thrombomodulin, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00020, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000007, intrinsic stability of activated TAFI (half-life): 6.3 min	Homo sapiens
R92K	mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively	Homo sapiens
R92K	mutant is not activated by thrombin, mutant is very efficiently activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.215, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000229, mutant is activated by plasmin with similar kinetics as wild-type, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00039, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000006, intrinsic stability of activated TAFI (half-life): 7.1 min	Homo sapiens
S90D/S94V/S90D	mutant is not activated by thrombin or by thrombin in the presence of thrombomodulin, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00004, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000005, intrinsic stability of activated TAFI (half-life): 5.9 min	Homo sapiens
S90P	mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively	Homo sapiens
S90P	mutant is not activated by thrombin, mutant is very efficiently activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.377, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000162, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00008, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000009, intrinsic stability of activated TAFI (half-life): 5.5 min	Homo sapiens
S94V	mutant is considerably more effectively activated by thrombin, mutant is also activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.328, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000232, mutation shows no effect on the activation by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.0003, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000006, intrinsic stability of activated TAFI (half-life): 6.1 min	Homo sapiens

General Stability

General Stability	Organism
intrinsic stability of activated TAFI (half-life): 6.8 min (wild-type)	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.000005	-	hippuryl-arginine	mutant S90D/S94V/S90D, activation of TAFI by plasmin	Homo sapiens
0.000005	-	hippuryl-arginine	wild-type, activation of TAFI by plasmin	Homo sapiens
0.000006	-	hippuryl-arginine	mutant R92K, activation of TAFI by plasmin	Homo sapiens
0.000006	-	hippuryl-arginine	mutant S94V, activation of TAFI by plasmin	Homo sapiens
0.000007	-	hippuryl-arginine	mutant P91S, activation of TAFI by plasmin	Homo sapiens
0.000009	-	hippuryl-arginine	mutant S90P, activation of TAFI by plasmin	Homo sapiens
0.00001	-	hippuryl-arginine	mutant A93V, activation of TAFI by plasmin	Homo sapiens
0.000162	-	p-anisylazoformyl-L-arginine	mutant S90P, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.000169	-	p-anisylazoformyl-L-arginine	mutant A93V, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.000178	-	p-anisylazoformyl-L-arginine	wild-type, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.000229	-	p-anisylazoformyl-L-arginine	mutant R92K, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.000232	-	p-anisylazoformyl-L-arginine	mutant S94V, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
using immunoaffinity chromatography in which monoclonal antibody MA-T4E3 is coupled to CNBr-activated Sepharose 4B	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
hippuryl-arginine + H2O	substrate is used to measure the TAFI activation by plasmin	Homo sapiens	hippuric acid + L-arginine	-	?
p-anisylazoformyl-L-arginine + H2O	substrate is used to measure the TAFI activation by thrombin and thrombin-thrombomodulin	Homo sapiens	p-anisylazoformic acid + L-arginine	-	?

Synonyms

Synonyms	Comment	Organism
TAFI	-	Homo sapiens
thrombin-activatable fibrinolysis inhibitor	-	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
0.00004	-	hippuryl-arginine	mutant S90D/S94V/S90D, activation of TAFI by plasmin	Homo sapiens
0.00008	-	hippuryl-arginine	mutant S90P, activation of TAFI by plasmin	Homo sapiens
0.0002	-	hippuryl-arginine	mutant P91S, activation of TAFI by plasmin	Homo sapiens
0.0003	-	hippuryl-arginine	mutant S94V, activation of TAFI by plasmin	Homo sapiens
0.00039	-	hippuryl-arginine	mutant R92K, activation of TAFI by plasmin	Homo sapiens
0.00042	-	hippuryl-arginine	wild-type, activation of TAFI by plasmin	Homo sapiens
0.00043	-	hippuryl-arginine	mutant A93V, activation of TAFI by plasmin	Homo sapiens
0.205	-	p-anisylazoformyl-L-arginine	mutant A93V, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.215	-	p-anisylazoformyl-L-arginine	mutant R92K, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.315	-	p-anisylazoformyl-L-arginine	wild-type, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.328	-	p-anisylazoformyl-L-arginine	mutant S94V, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens
0.377	-	p-anisylazoformyl-L-arginine	mutant S90P, activation of TAFI by thrombin in the presence of thrombomodulin	Homo sapiens

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Release 2023.1 (January 2023)