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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structural Studies of the Interaction of Crataeva tapia Bark Protein with Heparin and Other Glycosaminoglycans

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Author(s):
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Zhang, Fuming [1] ; Walcott, Benjamin [1] ; Zhou, Dongwen [2] ; Gustchina, Alla [2] ; Lasanajak, Yi [3] ; Smith, David F. [3] ; Ferreira, Rodrigo S. [4] ; Correia, Maria Tereza S. [5] ; Paiva, Patricia M. G. [5] ; Bovin, Nicolai V. [6] ; Wlodawer, Alexander [2] ; Oliva, Maria L. V. [4] ; Linhardt, Robert J. [1]
Total Authors: 13
Affiliation:
[1] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies, Dept B, Troy, NY 12180 - USA
[2] NCI, Macromol Crystallog Lab, Frederick, MD 21702 - USA
[3] Emory Univ, Sch Med, Dept Biochem, Glyc Ctr, Atlanta, GA 30322 - USA
[4] Univ Fed Sao Paulo, Dept Bioquim, BR-04044020 Sao Paulo - Brazil
[5] Univ Fed Pernambuco, Dept Bioquim, BR-50670901 Recife, PE - Brazil
[6] Russian Acad Sci, Inst Bioorgan Chem, Lab Carbohydrate Chem, Moscow 117997 - Russia
Total Affiliations: 6
Document type: Journal article
Source: BIOCHEMISTRY; v. 52, n. 12, p. 2148-2156, MAR 26 2013.
Web of Science Citations: 13
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 (K-D = 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. (AU)

FAPESP's process: 09/53766-5 - Proteins from plant source with selectivity for inhibition of mammalian enzymes and their role as an anti-inflammatory, antithrombotic, anti-diabetic and anti-tumor agent
Grantee:Maria Luiza Vilela Oliva
Support Opportunities: Research Projects - Thematic Grants