Therostasin, a novel clotting factor Xa inhibitor from the rhynchobdellid leech, Theromyzon tessulatum.
Therostasin is a potent naturally occurring tight-binding inhibitor of mammalian Factor Xa (K(i), 34 pm), isolated from the rhynchobdellid leech Theromyzon tessulatum. Therostasin is a cysteine-rich protein (8991 Da) consisting of 82 amino acid residues with 16 cysteine residues. Its amino acid sequence has been determined by a combination of techniques, including Edman degradation, enzymatic cleavage, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) on the native and s-beta-pyridylethylated compound. Sequence analysis reveals that it shares no significant homology with other Factor Xa inhibitors except for the putative reactive site. Moreover, it contains a signature pattern for proteins of the endothelin family, potent vasoconstrictors isolated in mammal and snake venom. Therostasin cDNA (825 bp) codes for a polypeptide of 82 amino acid residues preceded by 19 residues, representing a signal peptide sequence. As for the other known inhibitors of Factor Xa, therostasin is expressed and stored in the cells of the leech salivary glands.
Chopin
V
V
Laboratoire d'Endocrinologie des Annélides, UPRES-A 8017 CNRS, SN3, Université des Sciences et Technologie de Lille, F-59655 Villeneuve d'Ascq Cédex, France.
Salzet
M
M
Baert
J l
Jl
Vandenbulcke
F
F
Sautiére
P E
PE
Kerckaert
J P
JP
Malecha
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000302:isolation & purification; D001483:Base Sequence; D002850:Chromatography, Gel; D065427:Factor Xa Inhibitors; D007447:Invertebrate Hormones / Q000737:chemistry; D007865:Leeches / Q000235:genetics; D008322:Mammals; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D007447:Invertebrate Hormones; D011506:Proteins; D012333:RNA, Messenger; C063005:ghilanten; C093975:guamerin; C415823:therostasin protein, Theromyzon tessulatum; C053155:antistasin; C086021:hirustasin