Literature summary for 3.4.21.75 extracted from

Dahms, S.O.; Hardes, K.; Becker, G.L.; Steinmetzer, T.; Brandstetter, H.; Than, M.E.
X-ray structures of human furin in complex with competitive inhibitors (2014), ACS Chem. Biol., 9, 1113-1118.

Search for more literature for 3.4.21.75

Application

Application	Comment	Organism
drug development	furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression in HEK-293 cells	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with inhibitors m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine or phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, mixing of 7.5 mg/ml enzyme with 0.290 mM m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine and 3 mM phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, respectively, and 50 mM Tris, pH 8.5, 2.8 M sodium formate and 0.015 mM Cymal-7, at 30°C, displacement of the highly potent inhibitor m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine by competitive soaking with excessive amounts of the less potent phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, X-ray diffraction structure determination and analysis at 2.7 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in complex with inhibitors m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine or phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, mixing of 7.5 mg/ml enzyme with 0.290 mM m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine and 3 mM phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, respectively, and 50 mM Tris, pH 8.5, 2.8 M sodium formate and 0.015 mM Cymal-7, at 30°C, displacement of the highly potent inhibitor m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine by competitive soaking with excessive amounts of the less potent phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine, X-ray diffraction structure determination and analysis at 2.7 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine	a competitive, noncovalent inhibitor, binding structure, overview	Homo sapiens
additional information	peptidomimetic compounds based on a phenylacetyl-Arg-Val-Arg-4-(amidomethyl)benzamidine core structure belong to the strongest noncovalent enzyme inhibitors. Upon variation of the P5 position, dramatic changes of the Ki values are observed that cannot be explained by the known recognition motive. The Ki improves by approximately 2 orders of magnitude after addition of basic substituents, e.g., by modification of the Phac-moiety at P5 by a m- or p-guanidinomethyl group. Structure-guided drug design, overview	Homo sapiens
phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine	a competitive, noncovalent inhibitor, binding structure, overview	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	required	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P09958	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant enzyme 300fold from HEK-293 cells by metal affinity chromatography, inhibitor based affinity chromatography, and gel filtration	Homo sapiens

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
57	-	purified recombinant enzyme, pH 7.0, 37°C	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O	-	Homo sapiens	pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin	-	?

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	-	assay at	Homo sapiens

General Information

General Information	Comment	Organism
evolution	furin is a member of the pro-hormone/pro-protein convertase family of subtilisin-like endoproteinases	Homo sapiens