Document Type

Article

Original Publication Date

2007

Journal/Book/Conference Title

The Biophysical Journal

Volume

93

Issue

11

First Page

3963

Last Page

3976

DOI of Original Publication

10.1529/biophysj.106.100164

Comments

Originally published at http://dx.doi.org/10.1529/biophysj.106.100164

Under an Elsevier user license

Date of Submission

February 2015

Abstract

Abstract

Hemextin AB complex from the venom of Hemachatus haemachatus is the first known natural anticoagulant that specifically inhibits the enzymatic activity of blood coagulation factor VIIa in the absence of factor Xa. It is also the only known heterotetrameric complex of two three-finger toxins. Individually only hemextin A has mild anticoagulant activity, whereas hemextin B is inactive. However, hemextin B synergistically enhances the anticoagulant activity of hemextin A and their complex exhibits potent anticoagulant activity. In this study we characterized the nature of molecular interactions leading to the complex formation. Circular dichroism studies indicate the stabilization of β-sheet in the complex. Hemextin AB complex has an increased apparent molecular diameter in both gas and liquid phase techniques. The complex formation is enthalpically favorable and entropically unfavorable with a negative change in the heat capacity. Thus, the anticoagulant complex shows less structural flexibility than individual subunits. Both electrostatic and hydrophobic interactions are important for the complexation; the former driving the process and the latter helping in the stabilization of the tetramer. The tetramer dissociates into dimers and monomers with the increase in the ionic strength of the solution and also with increase in the glycerol concentration in the buffer. The two dimers formed under each of these conditions display distinct differences in their apparent molecular diameters and anticoagulant properties. Based on these results, we have proposed a model for this unique anticoagulant complex.

Rights

From The Biophysical Journal, Banerjee, Y., Lakshminarayanan, R., Vivekanandan, S., Biophysical Characterization of Anticoagulant Hemextin AB Complex from the Venom of Snake Hemachatus haemachatus, Vol. 93, Page 3963. Copyright © 2007 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.

Is Part Of

VCU Biochemistry and Molecular Biology Publications

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