An anticoagulant peptide from the human hookworm, Ancylostoma duodenale that inhibits coagulation factors Xa and XIa.
A full-length cDNA encoding an anticoagulant peptide, named AduNAP4, was cloned and identified from the human hookworm Ancylostoma duodenale. AduNAP4 has 104 amino acids including a predicted 23-residue signal peptide and shows <or= 50% similarity with other known nematode anticoagulant protein/peptide (NAP). AduNAP4 is extremely efficient at prolonging the activated partial thromboplastin time, and is an inhibitor of both fXa (K(i)=7.34+/-1.74 nM) and fXIa (K(i)=42.45+/-3.25 nM). No fXIa inhibitor has previously been described from other blood-feeding animals. Our results suggest that hookworms have evolved a potent mechanism that interferes with coagulation by inhibition of fXIa to facilitate its blood-feeding lifestyle.
Gan
Weiqiong
W
Department of Parasitology, Guangdong Medical College, Zhanjiang, China.
Deng
Li
L
Yang
Chen
C
He
Qingfeng
Q
Hu
Jingjing
J
Yin
Huan
H
Jin
Xian
X
Lu
Chengyu
C
Wu
Yamin
Y
Peng
Lifei
L
D000595:Amino Acid Sequence; D000722:Ancylostoma / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D000724:Ancylostomiasis / Q000097:blood / Q000150:complications / Q000469:parasitology; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification* / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D065427:Factor Xa Inhibitors; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000209:etiology / Q000469:parasitology; D015801:Helminth Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology
D000925:Anticoagulants; D017931:DNA Primers; D018076:DNA, Complementary; D018509:DNA, Helminth; D065427:Factor Xa Inhibitors; D015801:Helminth Proteins; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D015945:Factor XIa