Structural studies on the interaction of Crataeva tapia bark protein with heparin and other glycosaminoglycans

Authors
Zhang, F.
Wacott, B.
Zhou, D.
Gustchina, A.
Lasanajak, Y.
Smith, D.F.
Ferreira, R.S.
Correia, M T.S.
Paiva, P.M.G.
Bovin, N.V.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2013-03-26
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
Structural studies on the interaction of Crataeva tapia bark protein with heparin and other glycosaminoglycans, F. Zhang, B. Wacott, D. Zhou, A. Gustchina, Y. Lasanajak, D. F. Smith, R. S. Ferreira, M T. S. Correia, P. M.G. Paiva, N. V. Bovin, A. Wlodawer, M.L.V. Oliva, R. J. Linhardt, Biochemistry, 52, 2148−2156, 2013
Abstract
CrataBL, a protein isolated from Crataeva tapia bark, which is both a serine protease inhibitor and a lectin, has been previously shown to exhibit a number of interesting biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. Using a glycan array, we have now shown that only sulfated carbohydrates are effectively bound by CrataBL. Because this protein was recently shown to delay clot formation by impairing the intrinsic pathway of the coagulation cascade, we considered that its natural ligand might be heparin. Heparin is a glycosaminoglycan (GAG) that interacts with a number of proteins, including thrombin and antithrombin III, which have a critical, essential pharmacological role in regulating blood coagulation. We have thus employed surface plasmon resonance to improve our understanding of the binding interaction between the heparin polysaccharide and CrataBL. Kinetic analysis shows that CrataBL displays strong heparin binding affinity (KD = 49 nM). Competition studies using different size heparin-derived oligosaccharides showed that the binding of CrataBL to heparin is chain length-dependent. Full chain heparin with 40 saccharides or large oligosaccharides, having 16–18 saccharide residues, show strong binding affinity for CrataBL. Heparin-derived disaccharides through tetradecasaccharides show considerably lower binding affinity. Other highly sulfated GAGs, including chondroitin sulfate E and dermatan 4,6-disulfate, showed CrataBL binding affinity comparable to that of heparin. Less highly sulfated GAGs, heparan sulfate, chondroitin sulfate A and C, and dermatan sulfate displayed modest binding affinity as did chondroitin sulfate D. Studies using chemically modified heparin show that N-sulfo and 6-O-sulfo groups on heparin are essential for CrataBL–heparin interaction.
Description
Biochemistry, 52, 2148−2156
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
American Chemical Society (ACS)
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemistry
https://harc.rpi.edu/
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