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Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms.

Authors :
Earl ST
Richards R
Johnson LA
Flight S
Anderson S
Liao A
de Jersey J
Masci PP
Lavin MF
Source :
Biochimie [Biochimie] 2012 Feb; Vol. 94 (2), pp. 365-73. Date of Electronic Publication: 2011 Aug 11.
Publication Year :
2012

Abstract

As part of a wider study on Australian snake venom components, we have identified and characterised Kunitz-type protease inhibitors from the venoms of Oxyuranus scutellatus and Oxyuranus microlepidotus (Australian taipans) with plasma kallikrein inhibitory activity. Each inhibitor had a mass of 7 kDa and was purified from the venom as part of a protein complex. Mass spectrometry and N-terminal sequencing was employed to obtain amino acid sequence information for each inhibitor and a recombinant form of the O. scutellatus inhibitor, termed TSPI, was subsequently expressed and purified. TSPI was investigated for inhibition against a panel of 12 enzymes involved in haemostasis and estimates of the K(i) value determined for each enzyme. TSPI was found to be a broad spectrum inhibitor with most potent inhibitory activity observed against plasma kallikrein that corresponded to a K(i) of 0.057 ± 0.019 nM. TSPI also inhibited fibrinolysis in whole blood and prolonged the intrinsic clotting time. These inhibitors are also unique in that they appear to be found only in Oxyuranus sp. venoms.<br /> (Copyright © 2011. Published by Elsevier Masson SAS.)

Details

Language :
English
ISSN :
1638-6183
Volume :
94
Issue :
2
Database :
MEDLINE
Journal :
Biochimie
Publication Type :
Academic Journal
Accession number :
21843588
Full Text :
https://doi.org/10.1016/j.biochi.2011.08.003