Literature summary for 3.4.21.112 extracted from

Burri, D.; da Palma, J.; Seidah, N.; Zanotti, G.; Cendron, L.; Pasquato, A.; Kunz, S.
Differential recognition of old world and new world arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) (2013), J. Virol., 87, 6406-6414.

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Cloned(Commentary)

Cloned (Comment)	Organism
transient expression of wild-type and mutant enzymes in enzyme-deficient SRD12B cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
H249A	site-directed mutagenesis, catalytically inactive mutant showing no autoprocessing	Homo sapiens
Y285A	site-directed mutagenesis, molecular modeling	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.0025	-	Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0028	-	Ac-YISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0047	-	Ac-IYISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.005	-	Ac-YISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0056	-	Ac-YISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0057	-	Ac-YISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0074	-	Ac-IYISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0123	-	Ac-FISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.015	-	Ac-FISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0153	-	Ac-RRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0156	-	Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0212	-	Ac-YSSVSRKLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0226	-	Ac-IAVGRTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0228	-	Ac-RRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0274	-	Ac-RKLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0281	-	Ac-YSSVSRKLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0443	-	Ac-SFITRRLQ-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0504	-	Ac-AISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0564	-	Ac-RKLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.067	-	Ac-AISRRLL-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0784	-	Ac-SFITRRLQ-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0846	-	Ac-IAVGRTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.0967	-	Ac-RTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.0971	-	Ac-RRLQ-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant wild-type enzyme	Homo sapiens
0.2167	-	Ac-RTLK-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens
0.2263	-	Ac-RRLQ-7-amido-4-methylcoumarin	pH and temperature not specified in the publication, recombinant mutant Y285A	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
Ac-AISRRLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-AISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-FISRRLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-FISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-IAVGRTLK-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-IAVGRTLK + 7-amino-4-methylcoumarin	-	?
Ac-IYISRRLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-IYISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-QKSIAVGRTLK + 7-amino-4-methylcoumarin	-	?
Ac-RKLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-RKLL + 7-amino-4-methylcoumarin	-	?
Ac-RRLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-RRLL + 7-amino-4-methylcoumarin	-	?
Ac-RRLQ-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-RRLQ + 7-amino-4-methylcoumarin	-	?
Ac-RTLK-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-RTLK + 7-amino-4-methylcoumarin	-	?
Ac-SFITRRLQ-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-SFITRRLQ + 7-amino-4-methylcoumarin	-	?
Ac-YISRRLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-YISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-YSSVSRKLL-7-amido-4-methylcoumarin + H2O	Homo sapiens	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Ac-YSSVSRKLL + 7-amino-4-methylcoumarin	-	?
arenavirus envelope glycoprotein precursor + H2O	Homo sapiens	activation, F259A replacement at P7 of the viral protein substrate impaires the reaction, while replacement of with F does not affect enzyme processing. The catalytic pocket of the enzyme may interact with additional substrate residues distal from the actual cleavage site. Residue Y285 of the enzyme, located distal from the catalytic triad, is implicated in the molecular recognition of the aromatic signature residue at P7 and is crucial for efficient processing of OW and clade C NW arenavirus glycoprotein precursor	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q14703	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
Ac-AISRRLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-AISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-FISRRLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-FISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-IAVGRTLK-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-IAVGRTLK + 7-amino-4-methylcoumarin	-	?
Ac-IYISRRLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-IYISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-QKSIAVGRTLK + 7-amino-4-methylcoumarin	-	?
Ac-RKLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-RKLL + 7-amino-4-methylcoumarin	-	?
Ac-RRLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-RRLL + 7-amino-4-methylcoumarin	-	?
Ac-RRLQ-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-RRLQ + 7-amino-4-methylcoumarin	-	?
Ac-RTLK-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-RTLK + 7-amino-4-methylcoumarin	-	?
Ac-SFITRRLQ-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-SFITRRLQ + 7-amino-4-methylcoumarin	-	?
Ac-YISRRLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-YISRRLL + 7-amino-4-methylcoumarin	-	?
Ac-YSSVSRKLL-7-amido-4-methylcoumarin + H2O	an arenavirus envelope glycoprotein precursor protein-derived peptide substrate	Homo sapiens	Ac-YSSVSRKLL + 7-amino-4-methylcoumarin	-	?
arenavirus envelope glycoprotein precursor + H2O	activation, F259A replacement at P7 of the viral protein substrate impaires the reaction, while replacement of with F does not affect enzyme processing. The catalytic pocket of the enzyme may interact with additional substrate residues distal from the actual cleavage site. Residue Y285 of the enzyme, located distal from the catalytic triad, is implicated in the molecular recognition of the aromatic signature residue at P7 and is crucial for efficient processing of OW and clade C NW arenavirus glycoprotein precursor	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
SKI-1/S1P	-	Homo sapiens
subtilisin kexin isozyme 1/site 1 protease	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	modeling of the SKI-1/S1P catalytic pocket identifies Y285 as a residue that potentially interacts with arenavirus envelope glycoprotein precursor residue Y253. The the catalytic triad is formed by residues D218, H249, and S414	Homo sapiens
physiological function	the arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor by the cellular subtilisin kexin isozyme 1/site 1 protease	Homo sapiens