Purification, cloning and characterization of a metalloproteinase from Naja atra venom.
The complement system is a very important part of the immune system. Many snake venoms possess activities that influence the complement. A new metalloproteinase (termed atrase B) with anticomplementary activity was purified from Naja atra venom. Atrase B is a single chain glycoprotein with a molecular mass of 49.4 kDa and an isoelectric point of 9.7. Its N-terminal sequence shows high homology to those of metalloproteinases from cobra venoms. The cDNA sequence reveals that atrase B is a PIII class metalloproteinase. Atrase B slowly cleaves the Aα chain of fibrinogen. It also exhibits edema-inducing activity, but has no hemorrhagic activity and proteolytic activity against fibrin, azocasein, and N-benzoyl-l-arginine ethyl ester. Interestingly, atrase B inhibits activation of the complement classical and alternative pathways in a dose- and time-dependent manner. Complement components factor B and C6 are major targets for atrase B to cleave. Atrase B is the first identified SVMP that cleaves complement components factor B, C6, C7, and C8.
Sun
Qian-Yun
QY
Drug Screening Unit, The Key Laboratory of Chemistry for Natural Products, Guizhou Province and Chinese Academy of Sciences, 202 Sha-Chong South Road, Guiyang 550002, China. sunqy@hotmail.com
Bao
Juan
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D051056:Complement Inactivating Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D003165:Complement System Proteins / Q000378:metabolism; D004546:Elapid Venoms / Q000201:enzymology*; D017815:Elapidae / Q000378:metabolism*; D006801:Humans; D045726:Metalloproteases / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D008969:Molecular Sequence Data; D018675:Toxicity Tests
D051056:Complement Inactivating Agents; D004546:Elapid Venoms; D003165:Complement System Proteins; D045726:Metalloproteases