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3.4.21.21: coagulation factor VIIa

This is an abbreviated version!
For detailed information about coagulation factor VIIa, go to the full flat file.

Word Map on EC 3.4.21.21

Reaction

Selective cleavage of Arg-/-Ile bond in factor X to form factor Xa =

Synonyms

activated blood coagulation factor VII, activated coagulation factor VII, activated factor VII, blood coagulation factor VIIa, blood-coagulation factor VII, activated, blood-coagulation factor VIIa, coagulation factor VII, coagulation factor VII(a), coagulation FVII, Eptacog alfa, Factor VII, factor VIIa, factor VIIa-sTF, factor VIIa-TF, factor VIIa/tissue factor complex, FIIa, free factor VIIa, FVII, FVIIa, FVIIa-sTF, fVIIa/TF, FVIIc, human factor VIIa + TF, More, NovoSeven, procoagulant protein factor VII, recombinant factor VIIa, recombinant factor-activated VII, rFVII, rFVIIa, serine protease factor VIIa, Serum prothrombin conversion accelerator, soluble tissue factor/factor VIIa complex, sTF/VIIa, TF-FVIIa, TF/VIIa, tissue factor/factor VIIa, tissue factor/factor VIIa complex, vitamin K dependent clotting factor

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.21 coagulation factor VIIa

Engineering

Engineering on EC 3.4.21.21 - coagulation factor VIIa

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
306X
mutation studies show that the interaction between protein cofactor tissue factor and methionine-306 in the serine protease domain of FVIIa triggers the activation process and suggested some ensuing steps on the pathway to the active conformation
A294V
-
mutant enzyme shows delayed activation by activated factor X as well as reduced activity towards peptidyl and macromolecular substrates without impairing the catalytic efficiency of the triad
C164V/V299C-FVIIa
-
introduction of a new disulfide bridge between Cys-159 and an introduced Cys at position 299
D102Q
-
inactive mutant enzyme
D186A
-
turnover-number for activation of factor X is 5.5fold lower than that of the wild-type factor VII, Km-value for activation of factor X is 1.2fold lower than that of the wild-type factor VII
D343H
-
mutant enzyme shows no activity with methanesulfonyl-D-cyclohexylalanyl-butyl-arginine p-nitroanilide, factor X and factor IX
D72N
-
the mutant shows 13% of wild type FVIIa signaling activity towards protease-activated receptor 2
DELTA360-329
-
lower affinity for soluble tissue factor as compared to wild-type factor VIIa, 7fold smaller tissue factor-mediated acceleration of amidolytic activity compared to wild type factor VIIa
E154A
-
slightly increased Km-value and decreased turnover number compared to the wild-type enzyme
E154R
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
E296R
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
F256A
-
turnover-number and Km-value for activation of factor X are nearly identical to that of the wild-type factor VII
F374P
-
the specific clotting activity in presence of tissue factor is 50% of that of the wild-type factor VIIa
G372A
mutant G372A, both in the free and tissue factor-bound form, exhibit reduced cleavage of factor X and of D-Ile-Pro-Arg-4-nitroanilide (kcat increased compared to wild-type), and have increased Km values compared with wild-type FVIIa. Inhibition of mutant G372A +soluble tissue factor by 4-aminobenzamidine is characterized by a seven-fold higher Ki than obtained with wild-type. Crystallographic and modelling data suggest that the most active conformation of FVIIa depends on the backbone hydrogen bond between Gly372 and Arg315 in the 170 loop. Native and active site-inhibited mutant G372A binds soluble tissue factor with the same affinity as the corresponding forms of FVIIa
H101A
-
turnover-number for activation of factor X is 1.12fold lower than that of the wild-type factor VII, Km-value for activation of factor X is 1.23fold lower than that of the wild-type factor VII. Activation by factor Xa is significantly more slowly than that of wild-type enzyme. Tissue factor affinity and small substrate activity is similar to wild-type enzyme
H216A
-
mutant enzyme with decreased sensitivity to Zn2+ inhibition
H257A
-
mutant enzyme with decreased sensitivity to Zn2+ inhibition
K192E
-
completely ineffective mutant enzyme
K192Q
K305V
-
the ratio of turnover number to Km-value is 5.3fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
K337A
K341Q
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
L144A
L144A/R147A/D186A
-
turnover-number for activation of factor X is 239fold lower than that of the wild-type factor VII, Km-value for activation of factor X is 1.2fold higher than that of the wild-type factor VII
L280I/V299M-FVIIa
-
without description
L305V
-
mutant enzyme exhibits an increased rate of inhibition as compared with wild-type enzyme, both by D-Phe-Phe-Arg-chloromethyl ketone and antithombin III in presence of heparin. In complex with tissue factor both the amydolytic activity and the proteolytic activity are similar to that of the wild-type activity.The specific clotting activity in presence of tissue factor is 93% of that of the wild-type factor VIIa
L305V/K337A
-
the ratio of turnover number to Km-value is 6.3fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
L305V/M306D/D309S
-
amidylatic and proteolytic activity are virtually unaffected by the presence of tissue factor, 1.1fold increase. The specific clotting activity in presence of tissue factor is about 1% of that of the wild-type factor VIIa
M156K
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
M156Q
M298K
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
M298Q
M306D
M306N
-
amidolytic activity of the mutant enzyme is stimulated 7fold
M306N/N309S
-
amidolytic activity of the mutant enzyme is stimulated 1.5fold
M306S
-
amidolytic activity of the mutant enzyme is stimulated 9fold
M306T
-
amidolytic activity of the mutant enzyme is stimulated 12fold
N100A
-
turnover-number for activation of factor X is 3fold lower than that of the wild-type factor VII, Km-value for activation of factor X is 1.4fold lower than that of the wild-type factor VII
N100A/H101A/Y179A/F256A
-
turnover-number for activation of factor X is 3fold lower than that of the wild-type factor VII, Km-value for activation of factor X is nearly identical to that of the wild-type factor VII. Activation by factor Xa is significantly more slowly than that of wild-type enzyme
P10Q
-
site-directed mutagenesis, the mutant shows 2fold enhancement in membrane binding affinity over wild-type FVIIa
P10Q/K32E
-
site-directed mutagenesis, the mutant shows 27fold enhancement in membrane binding affinity over wild-type FVIIa, the double mutant displays a significantly improved procoagulant effect in haemophilic blood
P10Q/K32E/D33F/A34E
-
site-directed mutagenesis, the mutant shows 150-300fold enhancement in membrane binding affinity over wild-type FVIIa
P10Q/Q32E
-
mutant enzyme with elevated affinity for membrane. Phospholipid and cell-based assays show that mutant enzyme has an up to 40fold higher function then wild-type enzyme in both tissue-factor dependent reaction and in tissue factor independent reaction
Q143N
-
the mutant reduces interleukin-8 expression to background levels but maintains essentially normal pro-coagulant activity
Q143R
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
Q176G
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
Q217E
-
the mutant shows enhanced protease-activated receptor 2 activation
Q286R
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
Q40A
-
the mutant reduces interleukin-8 expression to background levels but maintains essentially normal pro-coagulant activity
Q40G
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
R147A
-
turnover-number for activation of factor X is 3.7fold lower than that of the wild-type factor VII, Km-value for activation of factor X is 1.2fold lower than that of the wild-type factor VII
R152Q
-
mutant enzyme shows no activity with methanesulfonyl-D-cyclohexylalanyl-butyl-arginine p-nitroanilide, factor X and factor IX
R353Q
in an observational study of 93 Japanese women 10 SNPs in relation to thrombosis or atherosclerosis are studied. Factor VII Arg353Gln and higher HDL-cholesterol (HDL-C) are linked to Arg/Arg carriers at higher levels
S344A
-
mutant enzyme shows no activity with methanesulfonyl-D-cyclohexylalanyl-butyl-arginine p-nitroanilide, factor X and factor IX
T151A
-
the mutant shows 13% of wild type FVIIa signaling activity towards protease-activated receptor 2
T151Q
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
T151S
-
the variant activates macromolecular coagulation substrates and supports signaling of the ternary tissue factor-FVIIa-Xa complex normally but is severely impaired in binary tissue factor-FVIIa-protease-activated receptor 2 signaling
T239A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T239G
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T239I
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T239Y
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
T293Q
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
T99A
-
the mutant shows 17% of wild type FVIIa signaling activity towards protease-activated receptor 2
T99Y
-
the mutation leads to enhanced protease-activated receptor 2 activation (2-3fold above the wild type FVIIa activity)
V154A
-
mutant enzyme shows reduced proteolytic activity towards factor X and undetectable activity towards factor IX
V154G
-
naturally occuring mutation, mutant enzyme with a zymogen-like form, markedly reduced activity towards peptidyl substrate and undetectable activity towards macromolecular substrates
V158D/D296V/M298Q
-
the ratio of turnover number to Km-value is 37.5fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
V158D/D296V/M298Q/K337A
-
the ratio of turnover number to Km-value is 56.3fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
V158D/D296V/M298Q/L305V
-
the ratio of turnover number to Km-value is 50fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
V158D/D296V/M298Q/L305V/L337
-
the ratio of turnover number to Km-value is 100fold higher than that of the wild-type enzyme with factor X as substrate, increased inhibition rate compared to wild-type enzyme with antithrobin in presence of heparin
V158D/E296V/M298Q
-
site-directed mutagenesis, FVIIa analogues with a stabilized activation domain and N-terminal insertion, the mutant shows increased activity compared to the wild-type enzyme
V158E
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
V21E
-
site-directed mutagenesis, activity and active site structure in comparison to the wild-type
V21N/E154I/M156Q
-
mutant enzyme with stabilized amino-terminal Ile16-Asp194 salt bridge and enhanced catalytic function
V299M-FVIIa
-
modification of the first Leu-X-Val motif by the introduction of Met in the third position
Y179A
-
turnover-number for activation of factor X is nearly identical to that of the wild-type factor VII, Km-value for activation of factor X is 1.6fold lower than that of the wild-type factor VII. Activation by factor Xa is significantly more slowly than that of wild-type enzyme. Tissue factor affinity and small substrate activity is similar to wild-type enzyme
additional information