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

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

Autor Zhang, Fuming Google Scholar
Walcott, Benjamin Google Scholar
Zhou, Dongwen Google Scholar
Gustchina, Alla Google Scholar
Lasanajak, Yi Google Scholar
Smith, David F. Google Scholar
Ferreira, Rodrigo S. Autor UNIFESP Google Scholar
Correia, Maria Tereza S. Google Scholar
Paiva, Patricia M. G. Google Scholar
Bovin, Nicolai V. Google Scholar
Wlodawer, Alexander Google Scholar
Oliva, Maria L. V. Autor UNIFESP Google Scholar
Linhardt, Robert J. Google Scholar
Instituição Rensselaer Polytech Inst
NCI
Emory Univ
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Pernambuco (UFPE)
Russian Acad Sci
Resumo 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.
Idioma Inglês
Financiador National Institutes of Health (NIH)
Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
Molecular and Cell Biology grant (Presidium RAS)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
National Institute of General Medical Sciences
Número do financiamento National Institutes of Health (NIH): GM-38060
FAPESP: 09/53766-5
National Institute of General Medical Sciences: GM62116
National Institute of General Medical Sciences: GM98791
Data 2013-03-26
Publicado em Biochemistry. Washington: Amer Chemical Soc, v. 52, n. 12, p. 2148-2156, 2013.
ISSN 0006-2960 (Sherpa/Romeo, fator de impacto)
Editor Amer Chemical Soc
Extensão 2148-2156
Fonte http://dx.doi.org/10.1021/bi400077b
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000316846800014
URI http://repositorio.unifesp.br/handle/11600/36101

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