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

Earl, Stephen T. H., Richards, Renee, Johnson, Lambro A., Flight, Simone, Anderson, Steven, Liao, Ann, de Jersey, John, Masci, Paul P. and Lavin, Martin F. (2012) Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms. Biochimie, 94 2: 365-373. doi:10.1016/j.biochi.2011.08.003


Author Earl, Stephen T. H.
Richards, Renee
Johnson, Lambro A.
Flight, Simone
Anderson, Steven
Liao, Ann
de Jersey, John
Masci, Paul P.
Lavin, Martin F.
Title Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms
Formatted title
Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms
Journal name Biochimie   Check publisher's open access policy
ISSN 0300-9084
1638-6183
Publication date 2012-02-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.biochi.2011.08.003
Volume 94
Issue 2
Start page 365
End page 373
Total pages 9
Editor R. Buckingham
Place of publication Issy les Moulineaux, France
Publisher Elsevier Masson
Language eng
Formatted 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 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 Ki 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.
Keyword Aprotinin
Kunitz-type inhibitor
Oxyuranus
Plasma kallikrein
Snake venom protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 11 August 2011.

 
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Created: Mon, 26 Mar 2012, 19:13:58 EST by Lucy O'Brien on behalf of UQ Centre for Clinical Research