A novel serine protease inhibitor from Bungarus fasciatus venom.
By Sephadex G-50 gel filtration, cation-exchange CM-Sephadex C-25 chromatography and reversed phase high-performance liquid chromatography (HPLC), a novel serine protease inhibitor named bungaruskunin was purified and characterized from venom of Bungarus fasciatus. Its cDNA was also cloned from the cDNA library of B. fasciatus venomous glands. The predicted precursor is composed of 83 amino acid (aa) residues including a 24-aa signal peptide and a 59-aa mature bungaruskunin. Bungaruskunin showed maximal similarity (64%) with the predicted serine protease inhibitor blackelin deduced from the cDNA sequence of the red-bellied black snake Pseudechis porphyriacus. Bungaruskunin is a Kunitz protease inhibitor with a conserved Kunitz domain and could exert inhibitory activity against trypsin, chymotrypsin, and elastase. By screening the cDNA library, two new B chains of beta-bungarotoxin are also identified. The overall structures of bungaruskunin and beta-bungarotoxin B chains are similar; especially they have highly conserved signal peptide sequences. These findings strongly suggest that snake Kunitz/BPTI protease inhibitors and neurotoxic homologs may have originated from a common ancestor.
Lu
Jia
J
Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Yang
Hailong
H
Yu
Haining
H
Gao
Weikai
W
Lai
Ren
R
Liu
Jingze
J
Liang
Xingcai
X
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002038:Bungarotoxins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017838:Bungarus / Q000378:metabolism*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism; D003001:Cloning, Molecular; D004546:Elapid Venoms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015723:Gene Library; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D002038:Bungarotoxins; D004546:Elapid Venoms; D015842:Serine Proteinase Inhibitors; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D014357:Trypsin