Arg15-Lys17-Arg18 turkey ovomucoid third domain inhibits human furin.
Turkey ovomucoid third domain with Leu18 in its reactive site is a potent inhibitor of many serine proteinases: subtilisins, chymotrypsins, and elastases. Previous studies showed that an L18K mutation made it a moderately strong inhibitor of trypsin, while an L18E mutation made it a strong inhibitor of Glu-specific Streptomyces griseus proteinase (GluSGP). For human furin substrates the consensus optimal sequence is RXKR decreases. Therefore the A15R, T17K, and L18R mutations were made in turkey ovomucoid third domain. The mutant inhibits human furin with a Ka of 1.1 x 10(7) M-1. As human furin catalyzes an obligatory step in human immunodeficiency virus proliferation, this inhibitor, along with the others already available, deserves further study.
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Department of Chemistry, Purdue University, West Lafayette, Indiana 47907.
Zhang
W
W
Molloy
S S
SS
Thomas
G
G
Ryan
K
K
Chiang
Y
Y
Anderson
S
S
Laskowski
M
M
D000595:Amino Acid Sequence; D000818:Animals; D045683:Furin; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010059:Ovomucin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D013381:Subtilisins / Q000037:antagonists & inhibitors*; D014422:Turkeys
D010446:Peptide Fragments; D010059:Ovomucin; D013381:Subtilisins; D045683:Furin