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Identification and characterisation of Kunitz-type plasma kallikrein inhibitors unique to Oxyuranus sp. snake venoms.
- 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.)
- Subjects :
- Amino Acid Sequence
Animals
Australia
Enzyme Inhibitors metabolism
Enzyme Inhibitors pharmacology
Fibrinolysis drug effects
Kinetics
Molecular Sequence Data
Molecular Weight
Plasma Kallikrein metabolism
Recombinant Proteins isolation & purification
Recombinant Proteins metabolism
Recombinant Proteins pharmacology
Sequence Alignment
Substrate Specificity
Thrombelastography
Whole Blood Coagulation Time
Elapid Venoms chemistry
Elapidae physiology
Enzyme Inhibitors isolation & purification
Plasma Kallikrein antagonists & inhibitors
Subjects
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