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Literature summary for 3.4.21.6 extracted from

  • Maignan, S.; Guilloteau, J.P.; Pouzieux, S.; Choi-Sledeski, Y.M.; Becker, M.R.; Klein, S.I.; Ewing, W.R.; Pauls, H.W.; Spada, A.P.; Mikol, V.
    Crystal structures of human factor Xa complexed with potent inhibitors (2000), J. Med. Chem., 43, 3226-3232.
    View publication on PubMed

Application

Application Comment Organism
pharmacology enyme is a potential target for development of antithrombotics, structure-based drug design approach usig the crystal structure of the enzyme-inhibitor complex Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified chymotrypsin treated enzyme lacking the first 45 amino acid residues, i.e. des(1-45)FXa, complexed with inhibitor, 8 mg/ml protein in 5 mM MES-NaOH, pH 6.0, 5 mM CaCl2, 0.001 mM inhibitor RPR128515, 0.003 ml mixed with equal volume of reservoir solution containing 18-20% PEG 600, 50 mM MES-NaOH, pH 5.7, hanging drop vapour diffusion method, 19°C, a few days, X-ray duffraction structure determination and analysis at 2.1 A resolution of crystals soaked in mother liquor containing 1-1.5 mM inhibitor and 5-10% dimethylformamide Homo sapiens
purified factor Xa, 8 mg/ml, in MES-NaOH, pH 6.0, 5 mM CaCl2, 0.001 mM inhibitor RPR128515, hanging drop vapour diffusion method, equal volume of 0.003 ml of protein and reservoir solution, the latter containing 18-20% PEG 600, 50 mM MES-NaOH, pH 5.7, 19°C, a few days, seeding cycles are necessary to improve size and shape of the crystals, X-ray diffraction structure determination and analysis at 2.1 A resolution Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information neutral groups such as chlorobenzohtiophene or chlorothiophene and basic groups such as benzamidine interact in the S1 pocket through the neutral group whereas the S4 pocket is occupied by the basic moiety Homo sapiens
RPR128515 compound contains a benzamidine moiety and surrogate of the basic group, binds in a canonical fashion typical for synthetic serine protease inhibitors, no direct hydrogen bonding with the carboxylate of Asp189 at the bottom of the S1 pocket, binding mode and inhibition mechanism; i.e. 3-[(3'-aminomethyl-biphenyl-4-carbonyl)-amino]-2-(3-carbamimidoyl-benzyl)-butyric acid methyl ester Homo sapiens
RPR131247 compound contains a benzamidine moiety and surrogate of the basic group, binds in a canonical fashion typical for synthetic serine protease inhibitors, no direct hydrogen bonding with the carboxylate of Asp189 at the bottom of the S1 pocket, binding mode and inhibition mechanism Homo sapiens
RPR132747 i.e. 3-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-benzamidine, non-peptide inhibitor based on a sulfonylpiperazinone scaffold Homo sapiens
RPR200095 i.e. 4-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-benzamidine Homo sapiens
RPR208707 compound contains a benzamidine moiety and surrogate of the basic group, binds in a canonical fashion typical for synthetic serine protease inhibitors, no direct hydrogen bonding with the carboxylate of Asp189 at the bottom of the S1 pocket, binding mode and inhibition mechanism Homo sapiens
RPR208815 compound contains a benzamidine moiety and surrogate of the basic group, binds in a canonical fashion typical for synthetic serine protease inhibitors, no direct hydrogen bonding with the carboxylate of Asp189 at the bottom of the S1 pocket, binding mode and inhibition mechanism Homo sapiens
RPR208944 i.e. 4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-1-[1-(2-hydroxy-ethyl)-1H-pyrrolo[3,2-c]pyridin-2-ylmethyl]-piperazin-2-one Homo sapiens
RPR209685 i.e. 4-[2-(5-chloro-thiophen-2-yl)-ethenesulfonyl]-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-piperazin-2-one Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens enzyme is involved in the coagulation cascade ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P00742
-
-

Reaction

Reaction Comment Organism Reaction ID
selective cleavage of Arg-/-Thr and then Arg-/-Ile bonds in prothrombin to form thrombin scutelarin has similar specificity Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
commercial preparation
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information enzyme is involved in the coagulation cascade Homo sapiens ?
-
?
prothrombin + H2O
-
Homo sapiens thrombin + ?
-
?

Synonyms

Synonyms Comment Organism
factor Xa
-
Homo sapiens
FXa
-
Homo sapiens
More the enzyme belongs to the peptidase family S1, i.e. trypsin family Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000007
-
RPR131247 with respect to factor Xa Homo sapiens
0.0000009
-
RPR128515
-
Homo sapiens
0.0000009
-
RPR128515 with respect to factor Xa Homo sapiens
0.0000011
-
RPR209685
-
Homo sapiens
0.0000013
-
RPR200095
-
Homo sapiens
0.0000018
-
RPR208707 with respect to factor Xa Homo sapiens
0.0000022
-
RPR208815 with respect to factor Xa Homo sapiens
0.000003
-
RPR208944
-
Homo sapiens
0.000018
-
RPR132747
-
Homo sapiens
0.003
-
RPR128515 above, with respect to thrombin Homo sapiens
0.004
-
RPR131247 above, with respect to thrombin Homo sapiens
0.004
-
RPR208815 above, with respect to thrombin Homo sapiens
0.004
-
RPR208707 above, with respect to thrombin Homo sapiens