Alsophinase, a new P-III metalloproteinase with α-fibrinogenolytic and hemorrhagic activity from the venom of the rear-fanged Puerto Rican Racer Alsophis portoricensis (Serpentes: Dipsadidae)

Biochimie
Caroline L Weldon, Stephen P Mackessy

Abstract

Metalloproteinases from snake venoms are often multi-domain enzymes involved in degradation of a variety of structural proteins. Hemorrhage and tissue necrosis are common manifestations of viperid envenomations in humans, largely due to the actions of prominent metalloproteinases, and envenomation by rear-fanged snakes may also cause hemorrhage. We purified the major metalloproteinase in Alsophis portoricensis (Puerto Rican Racer) venom through HPLC size exclusion and ion exchange chromatography. Named alsophinase, it is the first protein purified and characterized from the venom of Alsophis. Alsophinase is a single polypeptide chain protein, and based on mass, activity and complete inhibition by 1,10-phenanthroline, it is a class P-III snake venom member of the M12 ADAM family of metalloproteinases. Alsophinase has a molecular mass of 56.003kDa and an N-terminal sequence of QDTYLNAKKYIEFYLVVDNGMFxKYSxxFTV, with 67% sequence identity to a metalloproteinase isolated from venom of Philodryas olfersii (another rear-fanged species). Alsophinase rapidly catalyzed cleavage of only the Ala14-Leu15 bond of oxidized insulin B chain, had potent hemorrhagic activity in mice, and degraded only the α-subunit of human fibrinogen in vitro. Al...Continue Reading

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Citations

Dec 18, 2012·Molecular & Cellular Proteomics : MCP·Andreas BrustBryan G Fry
Mar 5, 2013·BMC Biology·Anthony J SaviolaStephen P Mackessy
Sep 15, 2012·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·María E PeichotoStephen P Mackessy
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Sep 26, 2015·Toxicon : Official Journal of the International Society on Toxinology·Zhixiao ZhangQuanshui Fan
Nov 26, 2013·Toxicon : Official Journal of the International Society on Toxinology·Adrijana LeonardiIgor Križaj
Mar 7, 2013·Toxicon : Official Journal of the International Society on Toxinology·Scott A WeinsteinDavid A Warrell
Jul 28, 2016·Toxins·Inácio L M Junqueira-de-AzevedoStephen P Mackessy
Sep 18, 2016·Integrative and Comparative Biology·Stephen P Mackessy, Anthony J Saviola
Oct 20, 2009·Toxicon : Official Journal of the International Society on Toxinology·Caroline L Weldon, Stephen P Mackessy
Dec 1, 2017·Toxins·Félix A Urra, Ramiro Araya-Maturana
Jan 12, 2016·PLoS Neglected Tropical Diseases·Tae Kwon KimAlbert Mulenga
Mar 30, 2017·The Journal of Pharmacology and Experimental Therapeutics·Priscila Hess LopesLuís Roberto C Gonçalves
Mar 22, 2019·Toxins·Konstantinos KalogeropoulosChristopher T Workman

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